flap endonucleases

Summary

Summary: Endonucleases that remove 5' DNA sequences from a DNA structure called a DNA flap. The DNA flap structure occurs in double-stranded DNA containing a single-stranded break where the 5' portion of the downstream strand is too long and overlaps the 3' end of the upstream strand. Flap endonucleases cleave the downstream strand of the overlap flap structure precisely after the first base-paired nucleotide, creating a ligatable nick.

Top Publications

  1. pmc Alternate pathways involving Sgs1/Top3, Mus81/ Mms4, and Srs2 prevent formation of toxic recombination intermediates from single-stranded gaps created by DNA replication
    Francis Fabre
    Unité mixte de recherche 217, Centre National de la Recherche Scientifique Commissariat à l Energie Atomique Département de Radiobiologie et Radiopathologie BP6, 92265 Fontenay aux Roses, France
    Proc Natl Acad Sci U S A 99:16887-92. 2002
  2. pmc Structures of human exonuclease 1 DNA complexes suggest a unified mechanism for nuclease family
    Jillian Orans
    Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA
    Cell 145:212-23. 2011
  3. pmc Human flap endonuclease structures, DNA double-base flipping, and a unified understanding of the FEN1 superfamily
    Susan E Tsutakawa
    Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA
    Cell 145:198-211. 2011
  4. pmc Polymerase dynamics at the eukaryotic DNA replication fork
    Peter M J Burgers
    Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 284:4041-5. 2009
  5. pmc Structural basis for recruitment of human flap endonuclease 1 to PCNA
    Shigeru Sakurai
    Structural Biology Laboratory, Nara Institute of Science and Technology, Takayama, Ikoma, Nara, Japan
    EMBO J 24:683-93. 2005
  6. pmc Human DNA2 is a mitochondrial nuclease/helicase for efficient processing of DNA replication and repair intermediates
    Li Zheng
    Department of Radiation Biology, City of Hope National Medical Center and Beckman Research Institute, Duarte, CA 91010, USA
    Mol Cell 32:325-36. 2008
  7. pmc DNA base excision repair: a mechanism of trinucleotide repeat expansion
    Yuan Liu
    Department of Chemistry and Biochemistry, Florida International University, Miami, FL 33199, USA
    Trends Biochem Sci 37:162-72. 2012
  8. pmc Pathways for Holliday junction processing during homologous recombination in Saccharomyces cerevisiae
    Thomas M Ashton
    Center for Healthy Aging, Department of Cellular and Molecular Medicine, Panum Institute 18 1, University of Copenhagen, DK 2200 Copenhagen, Denmark
    Mol Cell Biol 31:1921-33. 2011
  9. pmc Flap endonucleases pass 5'-flaps through a flexible arch using a disorder-thread-order mechanism to confer specificity for free 5'-ends
    NIKESH PATEL
    Centre for Chemical Biology, Department of Chemistry, Krebs Institute, University of Sheffield, Sheffield S3 7HF, UK
    Nucleic Acids Res 40:4507-19. 2012
  10. pmc Okazaki fragment maturation: nucleases take centre stage
    Li Zheng
    Department of Cancer Biology, City of Hope National Medical Center and Beckman Research Institute, Duarte, CA 91010, USA
    J Mol Cell Biol 3:23-30. 2011

Scientific Experts

Detail Information

Publications231 found, 100 shown here

  1. pmc Alternate pathways involving Sgs1/Top3, Mus81/ Mms4, and Srs2 prevent formation of toxic recombination intermediates from single-stranded gaps created by DNA replication
    Francis Fabre
    Unité mixte de recherche 217, Centre National de la Recherche Scientifique Commissariat à l Energie Atomique Département de Radiobiologie et Radiopathologie BP6, 92265 Fontenay aux Roses, France
    Proc Natl Acad Sci U S A 99:16887-92. 2002
    ..Our results suggest that Srs2 channels recombination intermediates back into the gap-filling route, whereas Sgs1Top3 and Mus81Mms4 are involved in recombination andor in replication to allow replication restart...
  2. pmc Structures of human exonuclease 1 DNA complexes suggest a unified mechanism for nuclease family
    Jillian Orans
    Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA
    Cell 145:212-23. 2011
    ..The relative arrangement of substrate binding sites in these enzymes provides an elegant solution to a complex geometrical puzzle of substrate recognition and processing...
  3. pmc Human flap endonuclease structures, DNA double-base flipping, and a unified understanding of the FEN1 superfamily
    Susan E Tsutakawa
    Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA
    Cell 145:198-211. 2011
    ....
  4. pmc Polymerase dynamics at the eukaryotic DNA replication fork
    Peter M J Burgers
    Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 284:4041-5. 2009
    ..In the more common short flap pathway, Pol delta coordinates with the flap endonuclease FEN1 to degrade initiator RNA, whereas in the long flap pathway, RNA removal is initiated by the Dna2 nuclease/helicase...
  5. pmc Structural basis for recruitment of human flap endonuclease 1 to PCNA
    Shigeru Sakurai
    Structural Biology Laboratory, Nara Institute of Science and Technology, Takayama, Ikoma, Nara, Japan
    EMBO J 24:683-93. 2005
    ..A hinge region present between the core domain and the C-terminal tail of FEN1 would play a role in switching the FEN1 orientation from an inactive to an active orientation...
  6. pmc Human DNA2 is a mitochondrial nuclease/helicase for efficient processing of DNA replication and repair intermediates
    Li Zheng
    Department of Radiation Biology, City of Hope National Medical Center and Beckman Research Institute, Duarte, CA 91010, USA
    Mol Cell 32:325-36. 2008
    ..Taken together, our studies illustrate an evolutionarily diversified role of hDNA2 in mitochondrial DNA replication and repair in a mammalian system...
  7. pmc DNA base excision repair: a mechanism of trinucleotide repeat expansion
    Yuan Liu
    Department of Chemistry and Biochemistry, Florida International University, Miami, FL 33199, USA
    Trends Biochem Sci 37:162-72. 2012
    ....
  8. pmc Pathways for Holliday junction processing during homologous recombination in Saccharomyces cerevisiae
    Thomas M Ashton
    Center for Healthy Aging, Department of Cellular and Molecular Medicine, Panum Institute 18 1, University of Copenhagen, DK 2200 Copenhagen, Denmark
    Mol Cell Biol 31:1921-33. 2011
    ..We propose that the Sgs1-Top3-Rmi1 complex constitutes the main pathway for the processing of HJ-containing HRR intermediates but that Mus81-Mms4 can also resolve these intermediates...
  9. pmc Flap endonucleases pass 5'-flaps through a flexible arch using a disorder-thread-order mechanism to confer specificity for free 5'-ends
    NIKESH PATEL
    Centre for Chemical Biology, Department of Chemistry, Krebs Institute, University of Sheffield, Sheffield S3 7HF, UK
    Nucleic Acids Res 40:4507-19. 2012
    b>Flap endonucleases (FENs), essential for DNA replication and repair, recognize and remove RNA or DNA 5'-flaps...
  10. pmc Okazaki fragment maturation: nucleases take centre stage
    Li Zheng
    Department of Cancer Biology, City of Hope National Medical Center and Beckman Research Institute, Duarte, CA 91010, USA
    J Mol Cell Biol 3:23-30. 2011
    ..On the other hand, mutations that impair editing out of polymerase α incorporation errors result in cancer displaying a strong mutator phenotype...
  11. ncbi Functional overlap between the structure-specific nucleases Yen1 and Mus81-Mms4 for DNA-damage repair in S. cerevisiae
    Miguel G Blanco
    London Research Institute, Cancer Research UK, South Mimms, Herts, UK
    DNA Repair (Amst) 9:394-402. 2010
    ..These findings indicate that Yen1 can act upon recombination/repair intermediates that arise in MUS81-defective cells following replication fork damage...
  12. pmc Functional regulation of FEN1 nuclease and its link to cancer
    Li Zheng
    Institute of Cell Biology and Genetics, College of Life Sciences, Zhejiang University, Hangzhou, China
    Nucleic Acids Res 39:781-94. 2011
    ..Lastly, we also review the biological significance of FEN1 as a tumor suppressor, with an emphasis on studies of human mutations and mouse models...
  13. ncbi Systematic genetic analysis with ordered arrays of yeast deletion mutants
    A H Tong
    Banting and Best Department of Medical Research, University of Toronto, Toronto ON, Canada M5G 1L6
    Science 294:2364-8. 2001
    ..Systematic application of this approach should produce a global map of gene function...
  14. pmc Potassium bromate, a potent DNA oxidizing agent, exacerbates germline repeat expansion in a fragile X premutation mouse model
    Ali Entezam
    Section on Genomic Structure and Function, Laboratory of Molecular and Cellular Biology, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, 8 Center Drive, Bethesda, MD 20892, USA
    Hum Mutat 31:611-6. 2010
    ..We show here that KBrO(3) increased both the level of 8-oxoG in the oocytes of treated animals and the germline expansion frequency. Our data thus suggest that oxidative damage may be a factor that could affect expansion risk in humans...
  15. pmc Unpairing and gating: sequence-independent substrate recognition by FEN superfamily nucleases
    Jane A Grasby
    Centre for Chemical Biology, Department of Chemistry, Krebs Institute, University of Sheffield, Sheffield S3 7HF, UK
    Trends Biochem Sci 37:74-84. 2012
    ..Superfamily members, such as flap endonucleases, exonuclease 1, DNA repair protein XPG, endonuclease GEN1 and the 5'-3'-exoribonucleases, play key roles in ..
  16. ncbi The role of the DNA sliding clamp in Okazaki fragment maturation in archaea and eukaryotes
    Thomas R Beattie
    Sir William Dunn School of Pathology, Oxford University, South Parks Road, Oxford OX1 3RE, UK
    Biochem Soc Trans 39:70-6. 2011
    ..This conformational malleability may be key to the co-ordination of these enzymes' activities...
  17. pmc The characterization of a mammalian DNA structure-specific endonuclease
    J J Harrington
    Department of Pathology, Stanford University School of Medicine, CA 94305 5324
    EMBO J 13:1235-46. 1994
    ..The endo- and exonuclease activities of FEN-1 are discussed in the context of DNA replication, recombination and repair...
  18. pmc Coordination between polymerase beta and FEN1 can modulate CAG repeat expansion
    Yuan Liu
    Laboratory of Structural Biology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    J Biol Chem 284:28352-66. 2009
    ..This is the first report illustrating that disruption of pol beta and FEN1 coordination during long-patch BER results in CAG repeat expansion...
  19. pmc The role of Holliday junction resolvases in the repair of spontaneous and induced DNA damage
    Neta Agmon
    Department of Molecular Microbiology and Biotechnology, Tel Aviv University, Ramat Aviv 69979, Israel
    Nucleic Acids Res 39:7009-19. 2011
    ..Finally, we show that yeast cells are unable to carry out meiosis in the absence of both resolvases. Our results show that both Yen1 and Mms4/Mus81 play important (although not identical) roles during vegetative growth and in meiosis...
  20. pmc The nucleotide sequence, DNA damage location, and protein stoichiometry influence the base excision repair outcome at CAG/CTG repeats
    Agathi Vasiliki Goula
    Department of Neurogenetics and Translational Medicine, Institute of Genetics and Molecular and Cellular Biology IGBMC, UMR 7104 CNRS INSERM UdS, Illkirch, France
    Biochemistry 51:3919-32. 2012
    ..Our results show that the BER stoichiometry, nucleotide sequence, and DNA damage position modulate repair outcome and suggest that a suboptimal long-patch BER activity promotes CAG/CTG repeat instability...
  21. pmc Specific synthetic lethal killing of RAD54B-deficient human colorectal cancer cells by FEN1 silencing
    Kirk J McManus
    Michael Smith Laboratories, University of British Columbia, 2185 East Mall, Vancouver, BC, Canada, V6T 1Z4
    Proc Natl Acad Sci U S A 106:3276-81. 2009
    ....
  22. ncbi Substrate recognition and catalysis by flap endonucleases and related enzymes
    Christopher G Tomlinson
    Centre for Chemical Biology, Department of Chemistry, Krebs Institute, University of Sheffield, Sheffield S3 7HF, UK
    Biochem Soc Trans 38:433-7. 2010
    FENs (flap endonucleases) and related FEN-like enzymes [EXO-1 (exonuclease-1), GEN-1 (gap endonuclease 1) and XPG (xeroderma pigmentosum complementation group G)] are a family of bivalent-metal-ion-dependent nucleases that catalyse ..
  23. ncbi The two DNA clamps Rad9/Rad1/Hus1 complex and proliferating cell nuclear antigen differentially regulate flap endonuclease 1 activity
    Erica Friedrich-Heineken
    Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich Irchel, Winterthurerstrasse 190, CH 8057, Zurich, Switzerland
    J Mol Biol 353:980-9. 2005
    ..Finally, acetylation of Fen1 by p300-HAT abolished the stimulatory effect of the 9-1-1 complex but not that of PCNA, suggesting a possible mechanism of regulation of this important repair pathway...
  24. pmc A junction branch point adjacent to a DNA backbone nick directs substrate cleavage by Saccharomyces cerevisiae Mus81-Mms4
    Kirk Tevebaugh Ehmsen
    Department of Microbiology, University of California, Davis, CA 95616 8665, USA
    Nucleic Acids Res 37:2026-36. 2009
    ..These findings underscore the significance of a nick adjacent to a branch point for Mus81-Mms4 incision...
  25. ncbi Interstrand disulfide crosslinking of DNA bases supports a double nucleotide unpairing mechanism for flap endonucleases
    Amanda Beddows
    Centre for Chemical Biology, Department of Chemistry, Krebs Institute, University of Sheffield, Sheffield, S3 7HF, UK
    Chem Commun (Camb) 48:8895-7. 2012
    b>Flap endonucleases (FENs) are proposed to select their target phosphate diester by unpairing the two terminal nucleotides of duplex...
  26. pmc Stoichiometry of base excision repair proteins correlates with increased somatic CAG instability in striatum over cerebellum in Huntington's disease transgenic mice
    Agathi Vassiliki Goula
    Department of Neurobiology and Genetics, Institute of Genetics and Molecular and Cellular Biology, UMR 7104 CNRS INSERM UdS, Illkirch, France
    PLoS Genet 5:e1000749. 2009
    ..We propose that the stoichiometry of BER enzymes is one critical factor underlying the tissue selectivity of somatic CAG expansion...
  27. ncbi Functional FEN1 polymorphisms are associated with DNA damage levels and lung cancer risk
    Ming Yang
    Department of Etiology and Carcinogenesis, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People s Republic of China
    Hum Mutat 30:1320-8. 2009
    ..These results highlight FEN1 as an important gene in human carcinogenesis and genetic polymorphisms in FEN1 confer susceptibility to lung cancer...
  28. ncbi Sequential and multistep substrate interrogation provides the scaffold for specificity in human flap endonuclease 1
    Mohamed A Sobhy
    Division of Biological and Environmental Sciences and Engineering, King Abdullah University of Science and Technology, Thuwal 23955, Saudi Arabia
    Cell Rep 3:1785-94. 2013
    ..Such mechanisms would also ensure the protection of DNA junctions from nonspecific bending and cleavage. ..
  29. pmc Amino acid Asp181 of 5'-flap endonuclease 1 is a useful target for chemotherapeutic development
    Harekrushna Panda
    Department of Anatomy and Cell Biology and UF Shands Cancer Center, University of Florida, Gainesville, Florida 32610, USA
    Biochemistry 48:9952-8. 2009
    ....
  30. pmc Overexpression and hypomethylation of flap endonuclease 1 gene in breast and other cancers
    Purnima Singh
    Department of Radiation Biology, City of Hope National Medical Center and Beckman Research Institute, Duarte, California 91010, USA
    Mol Cancer Res 6:1710-7. 2008
    ..The overexpression and promoter hypomethylation of FEN1 may serve as biomarkers for monitoring the progression of cancers...
  31. pmc Coordination of multiple enzyme activities by a single PCNA in archaeal Okazaki fragment maturation
    Thomas R Beattie
    Sir William Dunn School of Pathology, Oxford University, Oxford, UK
    EMBO J 31:1556-67. 2012
    ..Our data demonstrate that the most efficient coupling of activities occurs when a single PCNA ring organises PolB1, Fen1 and Lig1 into a complex...
  32. ncbi Cleavage of model replication forks by fission yeast Mus81-Eme1 and budding yeast Mus81-Mms4
    Matthew C Whitby
    Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, United Kingdom
    J Biol Chem 278:6928-35. 2003
    ..For most substrates the leading strand template is cleaved. The sole exception is a fork with a 5' single-stranded tail, which is cleaved in the lagging strand template...
  33. pmc Methylation of FEN1 suppresses nearby phosphorylation and facilitates PCNA binding
    Zhigang Guo
    Department of Cancer Biology, City of Hope National Medical Center and Beckman Research Institute, Duarte, California, USA
    Nat Chem Biol 6:766-73. 2010
    ..This consequently leads to a defect in Okazaki fragment maturation, a delay in cell cycle progression, impairment of DNA repair and a high frequency of genome-wide mutations...
  34. pmc Substrate channeling in mammalian base excision repair pathways: passing the baton
    Rajendra Prasad
    Laboratory of Structural Biology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    J Biol Chem 285:40479-88. 2010
    ..Instead, flap endonuclease 1 must recognize and bind to the intermediate in competition with other molecules...
  35. pmc Regulation of DNA replication and repair proteins through interaction with the front side of proliferating cell nuclear antigen
    Z O Jónsson
    Department of Veterinary Biochemistry, University Zurich Irchel, Winterthurerstrasse 190, CH 8057 Zurich, Switzerland
    EMBO J 17:2412-25. 1998
    ....
  36. pmc Evidence for a role of FEN1 in maintaining mitochondrial DNA integrity
    LIDZA KALIFA
    Department of Biology, University of Rochester, NY 14627, United States
    DNA Repair (Amst) 8:1242-9. 2009
    ..Our findings demonstrate that Rad27p/FEN1 is localized in the mitochondrial compartment of both yeast and mice and that Rad27p has a significant role in maintaining mtDNA integrity...
  37. pmc Nucleolar localization and dynamic roles of flap endonuclease 1 in ribosomal DNA replication and damage repair
    Zhigang Guo
    Department of Radiation Biology, City of Hope National Medical Center and Beckman Research Institute, 1500 East Duarte Road, Duarte, CA 91010, USA
    Mol Cell Biol 28:4310-9. 2008
    ..The replacement of Ser(187) by Ala, eliminating the only phosphorylation site, retains FEN1 in nucleoli. Both of the mutations cause UV sensitivity, impair cellular UV damage repair capacity, and decline overall cellular survivorship...
  38. pmc Saccharomyces cerevisiae Mus81-Mms4 is a catalytic, DNA structure-selective endonuclease
    Kirk Tevebaugh Ehmsen
    Section of Microbiology and Section of Molecular and Cellular Biology, University of California Davis, Davis, CA 95616 8665, USA
    Nucleic Acids Res 36:2182-95. 2008
    ..The endogenous complex purified in either modification state is negligibly active on Holliday junctions. Hence, Holliday junction incision activity in vitro cannot be attributed to the Mus81-Mms4 heterodimer in isolation...
  39. pmc Yeast Tdp1 and Rad1-Rad10 function as redundant pathways for repairing Top1 replicative damage
    John R Vance
    Plantaceutica, Incorporated, P O Box 12060, 99 Alexander Drive, Research Triangle Park, NC 27709 2060, USA
    Proc Natl Acad Sci U S A 99:13669-74. 2002
    ..Finally, we show that yeast lacking the Rad1-Rad10-related proteins Mus81-Mms4 display a unique pattern of camptothecin sensitivity and suggest a concerted model for the action of these endonucleases...
  40. ncbi Analysis of human flap endonuclease 1 mutants reveals a mechanism to prevent triplet repeat expansion
    Yuan Liu
    Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, New York 14642, USA
    J Biol Chem 278:13728-39. 2003
    ..In this way FEN1 employs endonuclease rather than exonuclease to prevent expansions. A model is presented describing the roles of DNA structure, DNA ligase I, and FEN1 in sequence expansion...
  41. pmc The mechanism of Mus81-Mms4 cleavage site selection distinguishes it from the homologous endonuclease Rad1-Rad10
    Suzanne A Bastin-Shanower
    Department of Molecular Biology and Biochemistry, CABM, Rutgers University, 679 Hoes Lane, Piscataway, NJ 08854, USA
    Mol Cell Biol 23:3487-96. 2003
    ..These data are most easily explained by a model in which the in vivo substrate of Mus81-Mms4 and Sgs1-Top3 is a 3' flap recombination intermediate downstream of replication fork collapse...
  42. ncbi Crystal structure of the rad9-rad1-hus1 DNA damage checkpoint complex--implications for clamp loading and regulation
    Andrew S Doré
    CR UK DNA Repair Enzymes Group, Section of Structural Biology, The Institute of Cancer Research, 237 Fulham Road, Chelsea, SW36JB London, UK
    Mol Cell 34:735-45. 2009
    ..Biochemical analysis reveals a single repair enzyme-binding site on 9-1-1 that can be blocked competitively by the PCNA-binding cell-cycle regulator p21(cip1/waf1)...
  43. ncbi Molecular mechanism of PCNA-dependent base excision repair
    Y Matsumoto
    Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA
    Prog Nucleic Acid Res Mol Biol 68:129-38. 2001
    ..Therefore, UNG2 and MYH may serve for replication-coupled base excision repair through the direct interaction with PCNA in the replication machinery...
  44. pmc Fen1 mutations that specifically disrupt its interaction with PCNA cause aneuploidy-associated cancer
    Li Zheng
    Department of Cancer Biology, City of Hope National Medical Center and Beckman Research Institute, Duarte, CA 91010, USA
    Cell Res 21:1052-67. 2011
    ..Thus, this study establishes an exemplary case for investigating the biological significance of protein-protein interactions by knock-in of a point mutation rather than knock-out of a whole gene...
  45. ncbi Incision-dependent and error-free repair of (CAG)(n)/(CTG)(n) hairpins in human cell extracts
    Caixia Hou
    Graduate Center for Toxicology and Markey Cancer Center, University of Kentucky College of Medicine, Lexington, Kentucky, USA
    Nat Struct Mol Biol 16:869-75. 2009
    ..We discuss the implications of these data for understanding the etiology of neurological diseases and trinucleotide repeat instability...
  46. pmc Flap endonuclease 1 mechanism analysis indicates flap base binding prior to threading
    Jason W Gloor
    Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA
    J Biol Chem 285:34922-31. 2010
    ..Apparently, interactions related to threading occur only when the flap is greater than two to four nucleotides long, implying that short flaps are cleaved without a threading requirement...
  47. pmc Trinucleotide repeat deletion via a unique hairpin bypass by DNA polymerase β and alternate flap cleavage by flap endonuclease 1
    Meng Xu
    Department of Chemistry and Biochemistry, Florida International University, 11200 SW 8th Street, Miami, FL 33199, USA
    Nucleic Acids Res 41:1684-97. 2013
    ..Our results provide new insight into the role of BER in modulating genome stability that is associated with human diseases...
  48. ncbi Brønsted analysis and rate-limiting steps for the T5 flap endonuclease catalyzed hydrolysis of exonucleolytic substrates
    Blanka Sengerová
    Centre for Chemical Biology, Department of Chemistry, University of Sheffield, Sheffield S3 7HF, UK
    Biochemistry 49:8085-93. 2010
    During replication and repair flap endonucleases (FENs) catalyze endonucleolytic and exonucleolytic (EXO) DNA hydrolyses...
  49. pmc Instability of CTG repeats is governed by the position of a DNA base lesion through base excision repair
    Yanhao Lai
    Department of Chemistry and Biochemistry, Florida International University, Miami, Florida, USA
    PLoS ONE 8:e56960. 2013
    ..Our study indicates that the position of a DNA base lesion governs whether TNR is expanded or deleted through BER...
  50. pmc Kinetics of endogenous mouse FEN1 in base excision repair
    Liv Kleppa
    Centre for Molecular Biology and Neuroscience and Institute of Clinical Medicine, Oslo University Hospital, Rikshospitalet, Norway
    Nucleic Acids Res 40:9044-59. 2012
    ..Inhibition of poly (ADP-ribose) polymerase 1 (PARP1) disrupts FEN1 accumulation at sites of DNA damage, indicating that PARP1 is required for FEN1 recruitment to DNA repair intermediates in BER...
  51. pmc The wonders of flap endonucleases: structure, function, mechanism and regulation
    L David Finger
    Department of Chemistry, Centre for Chemical Biology, Krebs Institute, University of Sheffield, Sheffield, S3 7HF, UK
    Subcell Biochem 62:301-26. 2012
    ....
  52. pmc Requirement for three novel protein complexes in the absence of the Sgs1 DNA helicase in Saccharomyces cerevisiae
    J R Mullen
    Department of Molecular Biology and Biochemistry, Center for Advanced Biotechnology and Medicine, Rutgers University, Piscataway, New Jersey 08855, USA
    Genetics 157:103-18. 2001
    ....
  53. ncbi Newly discovered archaebacterial flap endonucleases show a structure-specific mechanism for DNA substrate binding and catalysis resembling human flap endonuclease-1
    D J Hosfield
    Department of Molecular Biology, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California 92037, USA
    J Biol Chem 273:27154-61. 1998
    ..Thus, these archaeal enzymes may provide a means to dissect the specific binding and catalytic mechanisms of the entire FEN-1 family of structure-specific nucleases...
  54. pmc Proliferation failure and gamma radiation sensitivity of Fen1 null mutant mice at the blastocyst stage
    Elisabeth Larsen
    Centre for Molecular Biology and Neuroscience, Institute of Medical Microbiology, The National Hospital, University of Oslo, 0027 Oslo, Norway
    Mol Cell Biol 23:5346-53. 2003
    ..Our data thus provide in vivo evidence for an essential function of FEN1 in DNA repair, as well as in DNA replication...
  55. ncbi Multiple but dissectible functions of FEN-1 nucleases in nucleic acid processing, genome stability and diseases
    Binghui Shen
    Department of Radiation Biology, City of Hope National Medical Center and Beckman Research Institute, Duarte, CA 91010, USA
    Bioessays 27:717-29. 2005
    ..This review summarizes the knowledge gained through efforts in the past decade to define its structural elements for specific activities and possible pathological consequences of altered functions of this multirole player...
  56. ncbi The RAD2 domain of human exonuclease 1 exhibits 5' to 3' exonuclease and flap structure-specific endonuclease activities
    B I Lee
    Molecular Division, Lawrence Livermore National Laboratory, Livermore, California 94551, USA
    J Biol Chem 274:37763-9. 1999
    ..The nuclease activities of HEX1-N2 described here indicate functions for the EXO1-like proteins in replication, repair, and/or recombination that may overlap with human flap endonuclease-1...
  57. ncbi The identification and optimization of a N-hydroxy urea series of flap endonuclease 1 inhibitors
    L Nathan Tumey
    Athersys, Inc, 3201 Carnegie Ave, Cleveland, OH 44115, USA
    Bioorg Med Chem Lett 15:277-81. 2005
    ..To our knowledge, these are the most potent endonuclease inhibitors reported to date...
  58. ncbi FEN1 is overexpressed in testis, lung and brain tumors
    Teodora Nikolova
    Institute of Toxicology, University Medicine Mainz, 55131 Mainz, Germany
    Anticancer Res 29:2453-9. 2009
    ....
  59. pmc Acetylation of Dna2 endonuclease/helicase and flap endonuclease 1 by p300 promotes DNA stability by creating long flap intermediates
    Lata Balakrishnan
    Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA
    J Biol Chem 285:4398-404. 2010
    ..For example, altering the ratio between short and long flap Okazaki fragment processing would be a mechanism for better correction of the error-prone synthesis catalyzed by DNA polymerase alpha...
  60. pmc The 3'-flap pocket of human flap endonuclease 1 is critical for substrate binding and catalysis
    L David Finger
    Division of Radiation Biology, Graduate School of Biological Sciences, City of Hope National Medical Center and Beckman Research Institute, Duarte, CA 91010, USA
    J Biol Chem 284:22184-94. 2009
    ..Together the results indicate that the presence of a 3'-flap is the critical feature for efficient hFEN1 substrate recognition and catalysis...
  61. ncbi Flap endonuclease 1 is overexpressed in prostate cancer and is associated with a high Gleason score
    John S Lam
    Department of Urology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA 90095 1738, USA
    BJU Int 98:445-51. 2006
    ..1, the most aggressive clone generated from the hormone-refractory prostate cancer cell line CL1...
  62. pmc The human Rad9-Rad1-Hus1 checkpoint complex stimulates flap endonuclease 1
    Wensheng Wang
    Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA
    Proc Natl Acad Sci U S A 101:16762-7. 2004
    ..This suggests that 9-1-1 is a damage-specific activator of FEN1...
  63. ncbi Functional domains required for the Saccharomyces cerevisiae Mus81-Mms4 endonuclease complex formation and nuclear localization
    Yu Fu
    Department of Microbiology and Immunology, University of Saskatchewan, 107 Wiggins Road, Sask, S7N 5E5, Saskatoon, Canada
    DNA Repair (Amst) 2:1435-47. 2003
    ....
  64. pmc Long patch base excision repair proceeds via coordinated stimulation of the multienzyme DNA repair complex
    Lata Balakrishnan
    Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA
    J Biol Chem 284:15158-72. 2009
    ..Our results imply that this mechanism is still carried out, but in the context of a multienzyme complex that remains structurally intact during the repair process...
  65. ncbi Association of polymorphisms in base excision repair genes with the risk of breast cancer: a case-control study in North Indian women
    Amit Kumar Mitra
    Genotoxicity Laboratory, Toxicology Division, Central Drug Research Institute, Lucknow, Uttar Pradesh, India
    Oncol Res 17:127-35. 2008
    ..The results indicate that the polymorphisms rs1130409 (APEX1) and rs25487 (XRCC1) might be involved in contributing towards breast cancer susceptibility, while rs1799782 (XRCC1) might have protective influence...
  66. pmc Isolation of human Dna2 endonuclease and characterization of its enzymatic properties
    Jeong Hoon Kim
    National Creative Research Initiative Center for Cell Cycle Control, Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, 305 701, Korea
    Nucleic Acids Res 34:1854-64. 2006
    ..Based on this and other properties of hDna2, it is likely that this enzyme facilitates the removal of 5' and 3' regions in equilibrating flaps that are likely to arise during the processing of Okazaki fragments in human cells...
  67. pmc PCNA stimulates catalysis by structure-specific nucleases using two distinct mechanisms: substrate targeting and catalytic step
    Richard D Hutton
    Centre for Biomolecular Sciences and School of Physics, University of St Andrews, Fife, UK
    Nucleic Acids Res 36:6720-7. 2008
    ..This could provide a mechanism for the exquisite control of nuclease activity targeted to specific circumstances, such as replication forks or damaged DNA with pre-loaded PCNA...
  68. pmc p21Cip1/Waf1 disrupts the recruitment of human Fen1 by proliferating-cell nuclear antigen into the DNA replication complex
    U Chen
    Department of Pathology, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 93:11597-602. 1996
    ..Furthermore, overexpression of p21 can disrupt Fen1-PCNA interaction in vivo. Therefore, besides interfering with the processivity of polymerase delta-PCNA, p21 also uncouples Fen1 from the PCNA scaffold...
  69. ncbi Dna2p helicase/nuclease is a tracking protein, like FEN1, for flap cleavage during Okazaki fragment maturation
    Hui I Kao
    Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA
    J Biol Chem 279:50840-9. 2004
    ..We propose that the two nucleases both track, Dna2p first and then FEN1, to remove initiator RNA via long flap intermediates...
  70. pmc Functional overlap between Sgs1-Top3 and the Mms4-Mus81 endonuclease
    V Kaliraman
    Department of Molecular Biology and Biochemistry Center for Advanced Biotechnology and Medicine, Rutgers University, Piscataway, New Jersey 08854, USA
    Genes Dev 15:2730-40. 2001
    ..Repair of this double-strand break (DSB) by homologous recombination may be responsible for the elevated levels of sister chromatid exchange (SCE) found in BLM(-/-) cells...
  71. pmc Structure of an archaeal PCNA1-PCNA2-FEN1 complex: elucidating PCNA subunit and client enzyme specificity
    Andrew S Doré
    CR UK DNA Repair Enzymes Group, Section of Structural Biology, The Institute of Cancer Research, 237 Fulham Road, Chelsea, London, SW3 6JB, UK
    Nucleic Acids Res 34:4515-26. 2006
    ....
  72. pmc Complementary roles for exonuclease 1 and Flap endonuclease 1 in maintenance of triplet repeats
    Aarthy C Vallur
    Department of Immunology, University of Washington Medical School, Seattle, Washington 98195 7650, USA
    J Biol Chem 285:28514-9. 2010
    ..These results also suggest that unresolved G4 DNA may prevent key steps in normal post-replicative DNA processing...
  73. pmc Active site substitutions delineate distinct classes of eubacterial flap endonuclease
    Lee M Allen
    The University of Sheffield School of Medicine and Biomedical Sciences, Henry Wellcome Laboratories for Medical Research, Department of Infection and Immunity, Sheffield S102RX, UK
    Biochem J 418:285-92. 2009
    FENs (flap endonucleases) play essential roles in DNA replication, pivotally in the resolution of Okazaki fragments. In eubacteria, DNA PolI (polymerase I) contains a flap processing domain, the N-terminal 5'-->3' exonuclease...
  74. ncbi Inhibition of FEN-1 processing by DNA secondary structure at trinucleotide repeats
    C Spiro
    Department of Pharmacology, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA
    Mol Cell 4:1079-85. 1999
    ..However, when FEN-1 is absent from the cell, alternative pathways to simple inhibition of flap processing contribute to expansion...
  75. pmc Haploinsufficiency of yeast FEN1 causes instability of expanded CAG/CTG tracts in a length-dependent manner
    Jiahui Yang
    Department of Biology, Tufts University, Medford, MA 02155, USA
    Gene 393:110-5. 2007
    ....
  76. pmc Haploinsufficiency of Flap endonuclease (Fen1) leads to rapid tumor progression
    Melanie Kucherlapati
    Department of Medicine and Harvard Partners Center for Genetics and Genomics, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 99:9924-9. 2002
    ..The tumors from these mice show microsatellite instability. Because one copy of the Fen1 gene remained intact in tumors, Fen1 haploinsufficiency appears to lead to rapid progression of cancer...
  77. pmc Okazaki fragment processing: modulation of the strand displacement activity of DNA polymerase delta by the concerted action of replication protein A, proliferating cell nuclear antigen, and flap endonuclease-1
    G Maga
    Istituto di Genetica Biochimica ed Evoluzionistica Consiglio Nazionale delle Ricerche, I 27100 Pavia, Italy
    Proc Natl Acad Sci U S A 98:14298-303. 2001
    ..Our data support a model for Okazaki fragment processing where the strand displacement activity of DNA polymerase delta is modulated by the concerted action of PCNA, RP-A and Fen 1...
  78. pmc Significance of the dissociation of Dna2 by flap endonuclease 1 to Okazaki fragment processing in Saccharomyces cerevisiae
    Jason A Stewart
    Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA
    J Biol Chem 284:8283-91. 2009
    ..In summary, RPA, Dna2, and FEN1 have evolved highly coordinated binding properties enabling one protein to succeed the next for proper and efficient Okazaki flap processing...
  79. ncbi The "flap" endonuclease gene FEN1 is excluded as a candidate gene implicated in the CAG repeat expansion underlying Huntington disease
    C J Otto
    Department of Medical Genetics, University of Alberta, Edmonton, AB T6G 2H7, Canada
    Clin Genet 59:122-7. 2001
    ..The identification of a candidate gene(s) in HD or other CAG-expansion disorders implicated in TNR instability will elucidate the mechanism of expansion for this growing family of neurological disorders...
  80. ncbi The DNA repair endonuclease XPG binds to proliferating cell nuclear antigen (PCNA) and shares sequence elements with the PCNA-binding regions of FEN-1 and cyclin-dependent kinase inhibitor p21
    R Gary
    Life Sciences Division, Los Alamos National Laboratory, Los Alamos, New Mexico 87545, USA
    J Biol Chem 272:24522-9. 1997
    ..These results raise the possibility of a mechanistic linkage between excision and repair synthesis that is mediated by PCNA...
  81. pmc The Fen1 extrahelical 3'-flap pocket is conserved from archaea to human and regulates DNA substrate specificity
    Erica Friedrich-Heineken
    Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich, Winterthurerstrasse 190, CH 8057 Zurich, Switzerland
    Nucleic Acids Res 32:2520-8. 2004
    ..Human PCNA could stimulate the human Fen1 extrahelical 3'-flap pocket mutants but not restore their specificity. Thus the substrate specificity of Fen1 has been functionally conserved over a billion years from archaea to human...
  82. ncbi Increased expression and no mutation of the Flap endonuclease (FEN1) gene in human lung cancer
    Mitsuo Sato
    Department of Internal Medicine, Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, TX 75390 8593, USA
    Oncogene 22:7243-6. 2003
    ..Our results suggest that alterations of FEN1 are not likely to contribute to development of lung cancer...
  83. ncbi Flap endonuclease 1: a novel tumour suppresser protein
    Ghislaine Henneke
    Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich Irchel, Winterthurerstrasse 190, CH 8057 Zurich, Switzerland
    Trends Biochem Sci 28:384-90. 2003
  84. pmc Saccharomyces cerevisiae flap endonuclease 1 uses flap equilibration to maintain triplet repeat stability
    Yuan Liu
    Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA
    Mol Cell Biol 24:4049-64. 2004
    ..We present a model to explain how flap equilibration and the unique tracking mechanism of FEN1 can collaborate to remove TNR flaps and prevent repeat expansion...
  85. pmc Comparison of the catalytic parameters and reaction specificities of a phage and an archaeal flap endonuclease
    Ryan Williams
    Centre for Chemical Biology, Department of Chemistry, Krebs Institute, University of Sheffield, Sheffield, S3 7HF, UK
    J Mol Biol 371:34-48. 2007
    b>Flap endonucleases (FENs) catalyse the exonucleolytic hydrolysis of blunt-ended duplex DNA substrates and the endonucleolytic cleavage of 5'-bifurcated nucleic acids at the junction formed between single and double-stranded DNA...
  86. pmc Idling by DNA polymerase delta maintains a ligatable nick during lagging-strand DNA replication
    Parie Garg
    Department of Biochemistry, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Genes Dev 18:2764-73. 2004
    ..Consistent with the hypothesis that DNA polymerase epsilon is the leading-strand enzyme, we observed no idling by this enzyme and no cooperation with FEN1 for creating a ligatable nick...
  87. ncbi Mms4, a putative transcriptional (co)activator, protects Saccharomyces cerevisiae cells from endogenous and environmental DNA damage
    W Xiao
    Department of Microbiology, University of Saskatchewan, Saskatoon, Canada
    Mol Gen Genet 257:614-23. 1998
    ..These results collectively suggest that Mms4 may function as a transcriptional (co)activator and play an important role in DNA repair and/or synthesis...
  88. pmc The trans-autostimulatory activity of Rad27 suppresses dna2 defects in Okazaki fragment processing
    Palinda Ruvan Munashingha
    Center for DNA Replication and Genome Instability, Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Korea
    J Biol Chem 287:8675-87. 2012
    ..Our findings provide further insight into how Dna2 and Rad27 jointly affect the processing of Okazaki fragments in eukaryotes...
  89. ncbi Down-regulation of human FEN-1 gene expression during differentiation of promyelocytic leukemia cells
    I S Kim
    Department of Natural Sciences Chemistry Section, Catholic University of Korea College of Medicine, Seoul, Korea
    Exp Mol Med 30:252-6. 1998
    ..These results demonstrate that the FEN-1 gene expression is up-regulated during entrance into the mitotic cell cycle and down-regulated in nongrowing cells, as in the case of differentiated promyelocytic leukemia cells...
  90. ncbi Huntingtin triplet-repeat locus is stable under long-term Fen1 knockdown in human cells
    Svein Erik Moe
    Centre for Molecular Biology and Neuroscience CMBN, and Department of Anatomy, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
    J Neurosci Methods 171:233-8. 2008
    ..Our results argue against a role for Fen1 in triggering Huntingtin triplet expansion in human cells...
  91. ncbi FEN1 contributes to telomere stability in ALT-positive tumor cells
    A Saharia
    Department of Cell Biology and Physiology, Washington University School of Medicine, Saint Louis, MO 63110, USA
    Oncogene 28:1162-7. 2009
    ....
  92. ncbi Evidence that DNA damage detection machinery participates in DNA repair
    Christopher E Helt
    Department of Radiation Oncology, School of Medicine and Dentistry, The University of Rochester, Rochester, New York 14642, USA
    Cell Cycle 4:529-32. 2005
    ..Furthermore, preliminary results indicate a stimulation of DNA ligase I. In this review, the likely direct participation of 9-1-1 in DNA repair is discussed...
  93. pmc RecQ helicase, Sgs1, and XPF family endonuclease, Mus81-Mms4, resolve aberrant joint molecules during meiotic recombination
    Steve D Oh
    Department of Microbiology, University of California, Davis, One Shields Avenue, Davis, CA 95616, USA
    Mol Cell 31:324-36. 2008
    ..We conclude that Sgs1 and Mus81-Mms4 collaborate to eliminate aberrant JMs, whereas as-yet-unidentified enzymes process normal JMs...
  94. pmc Distinct activities of exonuclease 1 and flap endonuclease 1 at telomeric g4 DNA
    Aarthy C Vallur
    Department of Immunology, University of Washington School of Medicine, Seattle, Washington, United States of America
    PLoS ONE 5:e8908. 2010
    ..Telomeres are composed of G-rich repeats that readily form G4 DNA. We recently showed that human EXO1 and FEN1 exhibit distinct activities on G4 DNA substrates representative of intermediates in immunoglobulin class switch recombination...
  95. pmc Differential processing of leading- and lagging-strand ends at Saccharomyces cerevisiae telomeres revealed by the absence of Rad27p nuclease
    Julie Parenteau
    Departement De Microbiologie et Infectiologie, Faculte de Medecine, Université de Sherbooke, Sherbooke, Quebec J1H 5N4, Canada
    Genetics 162:1583-94. 2002
    ..These data further support the notion that chromosome ends have differential requirements for end processing, depending on whether the ends were replicated by leading- or lagging-strand synthesis...
  96. ncbi The identification and optimization of 2,4-diketobutyric acids as flap endonuclease 1 inhibitors
    L Nathan Tumey
    Athersys, Inc, 3201 Carnegie Ave, Cleveland, OH 44115, USA
    Bioorg Med Chem Lett 14:4915-8. 2004
    ..In this report, we describe the identification and SAR of a series of 2,4-diketobutyric acid FEN1 inhibitors...
  97. ncbi Cell cycle-dependent and DNA damage-inducible nuclear localization of FEN-1 nuclease is consistent with its dual functions in DNA replication and repair
    J Qiu
    Department of Cell and Tumor Biology, City of Hope National Medical Center, Duarte, CA 91010, USA
    J Biol Chem 276:4901-8. 2001
    ..Yeast RAD27Delta cells transformed with human mutant M(krk) survived poorly upon methyl methanesulfonate treatment or when they were incubated at an elevated temperature...
  98. pmc Studies with the human cohesin establishment factor, ChlR1. Association of ChlR1 with Ctf18-RFC and Fen1
    Andrea Farina
    Program of Molecular Biology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA
    J Biol Chem 283:20925-36. 2008
    ..These findings are consistent with a role of hChlR1 in the establishment of sister chromatid cohesion and suggest that its action may contribute to lagging strand processing events important in cohesion...
  99. ncbi Interaction and stimulation of human FEN-1 nuclease activities by heterogeneous nuclear ribonucleoprotein A1 in alpha-segment processing during Okazaki fragment maturation
    Qing Chai
    Division of Molecular Biology, City of Hope National Medical Center and Beckman Research Institute, Duarte, California 91010, USA
    Biochemistry 42:15045-52. 2003
    ..With longer flap substrates the hnRNP A1 effect is more modest and is suppressed by the addition of RPA. A model is provided to explain the possible in vivo role of this interaction and activity in Okazaki fragment maturation...
  100. ncbi Concerted action of exonuclease and Gap-dependent endonuclease activities of FEN-1 contributes to the resolution of triplet repeat sequences (CTG)n- and (GAA)n-derived secondary structures formed during maturation of Okazaki fragments
    Purnima Singh
    Department of Radiation Biology, City of Hope National Medical Center and Beckman Research Institute, Duarte, California 91010, USA
    J Biol Chem 282:3465-77. 2007
    ..A model is presented to explain how the concerted action of EXO and GEN activities may contribute to resolving structured flaps, thereby preventing their expansion in the genome...
  101. pmc Human flap endonuclease I is in complex with telomerase and is required for telomerase-mediated telomere maintenance
    Shilpa Sampathi
    Washington, Wyoming, Alaska, Montana, Idaho Medical Education Program, Washington State University, Spokane, Washington 99210, USA
    J Biol Chem 284:3682-90. 2009
    ..This is, to our knowledge, the first evidence that FEN1 and telomerase physically co-exist as a complex and that FEN1 can regulate telomerase activity at telomeres in mammalian cells...

Research Grants22

  1. DNA POLYMERASE IN NORMAL AND NEOPLASTIC HUMAN CELLS
    Teresa Wang; Fiscal Year: 2006
    ..Results from these studies will contribute to our understanding of one of the molecular bases underlying the mechanisms that initiate the genomic instability and carcinogenesis. ..
  2. FEN-1 and PCNA Complexes and Human Genome Stability
    John A Tainer; Fiscal Year: 2013
    ..The results will also clarify mechanisms whereby loss of the functions of these coordinated complexes, which act in DNA replication and repair processes, may lead to inheritable genetic defects and the cancer initiation. ..
  3. Functional Analysis of FEN-1 Nuclease in Genome Stability and Cancers
    Binghui Shen; Fiscal Year: 2013
    ....
  4. Genome stability maintenance factors in early HIV-1 infection
    LUBBERTUS MULDER; Fiscal Year: 2009
    ..This can then translate not only in the precious expansion of our knowledge about the viral biology but possibly in the discovery of amenable anti- retroviral targets. ..
  5. DNA Recombination/Repair Mechanisms in Memory
    SANDRA PENA DE ORTIZ; Fiscal Year: 2011
    ....
  6. DNA BASE EXCISION REPAIR IN PLASMODIUM FALCIPARUM
    THEODORE TARASCHI; Fiscal Year: 2005
    ..falciparum and mammalian cells to develop new strategies for antimalarial therapy. ..
  7. STRUCTURE/FUNCTION OF A DNA REPAIR ENDONUCLEASE
    Binghui Shen; Fiscal Year: 2001
    ..b>Flap endonucleases (FEN), in contrast, can recognize the damaged DNA fragments and cleave them without accessory proteins...
  8. STRUCTURE SPECIFIC NUCLEASES IN GENOMIC INSTABILITY
    Min Park; Fiscal Year: 2001
    ..The results of this study will provide a detailed mechanistic understanding of the trinucleotide repeat instablitlity in mammalian genome. ..
  9. GENETIC INSTABILITY AND TRIPLET REPEAT DISEASES IN AGING
    MYRON GOODMAN; Fiscal Year: 2002
    ..The chromosomal, tissue and organismal effects of these mutations will also be examined in animals as a function of age. Project 3 will require the use of both the Mouse core and the Biochemical-Analytical Core. ..
  10. SITE SPECIFIC DNA DAMAGE AND GENOMIC INSTABILITY IN MAMM
    ROY SARGENT; Fiscal Year: 2003
    ..3) To investigate the role of the structure-specific nucleases, ERCC1/XPF, XPG, and FEN-1 on processing DNA structures and genomic instability. ..
  11. Characterization of a Flap-Endonuclease-1 Mutant Mouse Model
    Valerie Chavez; Fiscal Year: 2007
    ..Aim 1: Determine the role of MMP in extracellular CII degradation and augmentation of MHCII mediated presentation of CII epitopes by DC. Aim 2: Determine the role of cathepsin K in the processing and presentation of native CII by DC. ..
  12. GENETIC VARIATION IN HUMAN NHEJ DNA REPAIR GENES
    Carl Anderson; Fiscal Year: 2005
    ..This study also will provide a moderately dense set of mapped polymorphic markers within the five know NHEJ genes for subsequence linkage studies that could reveal subtle effects and more complex allele interactions. ..
  13. FEN-1/WRN Complex in Prevention of Genetic Diseases
    L Finger; Fiscal Year: 2008
    ....
  14. Genetic Recombination/Genomic Rearrangements Conference
    LORRAINE SYMINGTON; Fiscal Year: 2005
    ..abstract_text> ..
  15. FUNCTION OF PCNA IN CELLULAR DNA REPAIR
    Yoshihiro Matsumoto; Fiscal Year: 2001
    ..abstract_text> ..
  16. Mechanisms of Mitotic Recombination
    JEFF JOSEPH SEKELSKY; Fiscal Year: 2010
    ..These studies will enhance our understanding of mechanisms of mitotic crossing over and the role that the important tumor suppressor protein BLM plays in preventing mitotic crossing over. ..
  17. Coordination of the late steps of human nucleotide excision repair
    ORLANDO D SCHARER; Fiscal Year: 2010
    ..Since NER proteins also contribute to the resistance of tumor cells to anti-cancer agents our investigations may also provide new targets for anti- tumor therapy. ..
  18. Structure/Function Studies of Quinone Reductase 2
    Zhongtao Zhang; Fiscal Year: 2009
    ....
  19. STRUCTURE/FUNCTION OF YEAST DNA POLYMERASE DELTA
    PETER BURGERS; Fiscal Year: 2002
    ..Improper regulation of these processes in humans may lead to cancer. ..
  20. MECHANISM OF BASE EXCISION REPAIR IN HIGHER EUKARYOTES
    Yoshihiro Matsumoto; Fiscal Year: 2003
    ..However, since the 5'-incised AP site is a unique DNA structure in this repair system, this study will add a new insight to the functions of these versatile proteins. ..
  21. Genetic Recombination and Chromosome Rearrangements
    LORRAINE SYMINGTON; Fiscal Year: 2007
    ..Much of the conference will be devoted to topics of concern both to the National Cancer Institute and to the Institute of Environmental and Health Sciences. [unreadable] [unreadable] [unreadable] [unreadable]..
  22. Mechanisms of Double-strand Break Repair in Yeast
    LORRAINE SYMINGTON; Fiscal Year: 2009
    ..The last aim includes in vitro studies to identify preferred DNA substrates for Rad55:Rad57 binding and stabilization of the Rad51 nucleoprotein by Rad55:Rad57 in the presence or absence of Srs2. ..