FEN1

Summary

Gene Symbol: FEN1
Description: flap structure-specific endonuclease 1
Alias: FEN-1, MF1, RAD2, flap endonuclease 1, DNase IV, maturation factor-1
Species: human
Products:     FEN1

Top Publications

  1. Spiro C, Pelletier R, Rolfsmeier M, Dixon M, Lahue R, Gupta G, et al. Inhibition of FEN-1 processing by DNA secondary structure at trinucleotide repeats. Mol Cell. 1999;4:1079-85 pubmed
    ..However, when FEN-1 is absent from the cell, alternative pathways to simple inhibition of flap processing contribute to expansion. ..
  2. Zheng L, Zhou M, Chai Q, Parrish J, Xue D, Patrick S, et al. Novel function of the flap endonuclease 1 complex in processing stalled DNA replication forks. EMBO Rep. 2005;6:83-9 pubmed
    ..Here, we identify a novel gap endonuclease (GEN) activity of human flap endonuclease 1 (FEN-1), critical in resolving stalled replication fork...
  3. Finger L, Blanchard M, Theimer C, Sengerová B, Singh P, Chavez V, et al. The 3'-flap pocket of human flap endonuclease 1 is critical for substrate binding and catalysis. J Biol Chem. 2009;284:22184-94 pubmed publisher
    b>Flap endonuclease 1 (FEN1) proteins, which are present in all kingdoms of life, catalyze the sequence-independent hydrolysis of the bifurcated nucleic acid intermediates formed during DNA replication and repair...
  4. Tsutakawa S, Classen S, Chapados B, Arvai A, Finger L, Guenther G, et al. Human flap endonuclease structures, DNA double-base flipping, and a unified understanding of the FEN1 superfamily. Cell. 2011;145:198-211 pubmed publisher
    Flap endonuclease (FEN1), essential for DNA replication and repair, removes RNA and DNA 5' flaps...
  5. Saharia A, Guittat L, Crocker S, Lim A, Steffen M, Kulkarni S, et al. Flap endonuclease 1 contributes to telomere stability. Curr Biol. 2008;18:496-500 pubmed publisher
    ..b>Flap endonuclease 1 (FEN1) is a protein that plays a role in lagging-strand DNA replication, base excision repair, homologous ..
  6. Guo Z, Qian L, Liu R, Dai H, Zhou M, Zheng L, et al. Nucleolar localization and dynamic roles of flap endonuclease 1 in ribosomal DNA replication and damage repair. Mol Cell Biol. 2008;28:4310-9 pubmed publisher
    ..and our recent findings of its roles in genome stability and cancer avoidance of the structure-specific flap endonuclease 1 (FEN1), its cellular compartmentalization and dynamics corresponding to its involvement in various DNA ..
  7. Singh P, Yang M, Dai H, Yu D, Huang Q, Tan W, et al. Overexpression and hypomethylation of flap endonuclease 1 gene in breast and other cancers. Mol Cancer Res. 2008;6:1710-7 pubmed publisher
    b>Flap endonuclease 1 (FEN1) is a structure-specific nuclease best known for its critical roles in Okazaki fragment maturation, DNA repair, and apoptosis-induced DNA fragmentation...
  8. Cho I, Kim D, Kang Y, Lee C, Amangyelid T, Nguyen T, et al. Human replication factor C stimulates flap endonuclease 1. J Biol Chem. 2009;284:10387-99 pubmed publisher
    b>Flap endonuclease 1 (FEN1) is the enzyme responsible for specifically removing the flap structure produced during DNA replication, repair, and recombination...
  9. Sharma S, Otterlei M, Sommers J, Driscoll H, Dianov G, Kao H, et al. WRN helicase and FEN-1 form a complex upon replication arrest and together process branchmigrating DNA structures associated with the replication fork. Mol Biol Cell. 2004;15:734-50 pubmed
    ..These results provide evidence for an interaction between WRN and FEN-1 in vivo and suggest that these proteins function together to process DNA structures associated with the replication fork. ..

More Information

Publications74

  1. Henneke G, Koundrioukoff S, Hubscher U. Phosphorylation of human Fen1 by cyclin-dependent kinase modulates its role in replication fork regulation. Oncogene. 2003;22:4301-13 pubmed
    Cyclin-dependent kinase (Cdk) Cdk1-Cyclin A can phosphorylate Flap endonuclease 1 (Fen1), a key-enzyme of the DNA replication machinery, in late S phase. Cdk1-cyclin A forms a complex in vitro and in vivo with Fen1...
  2. Yang M, Guo H, Wu C, He Y, Yu D, Zhou L, et al. Functional FEN1 polymorphisms are associated with DNA damage levels and lung cancer risk. Hum Mutat. 2009;30:1320-8 pubmed publisher
    b>Flap endonuclease 1 (FEN1) is a key enzyme in maintaining genomic stability and protecting against carcinogenesis. This study investigated whether functional variations in FEN1 gene are associated with DNA damage and lung cancer risk...
  3. Saharia A, Teasley D, Duxin J, Dao B, Chiappinelli K, Stewart S. FEN1 ensures telomere stability by facilitating replication fork re-initiation. J Biol Chem. 2010;285:27057-66 pubmed publisher
    ..Recently, we demonstrated that the DNA replication and repair protein Flap endonuclease 1 (FEN1) is required for replication of lagging strand telomeres...
  4. Brosh R, Driscoll H, Dianov G, Sommers J. Biochemical characterization of the WRN-FEN-1 functional interaction. Biochemistry. 2002;41:12204-16 pubmed
    ..The ability of WRN to facilitate FEN-1 cleavage of DNA replication/repair intermediates may be important for the role of WRN in the maintenance of genomic stability. ..
  5. Brosh R, von Kobbe C, Sommers J, Karmakar P, Opresko P, Piotrowski J, et al. Werner syndrome protein interacts with human flap endonuclease 1 and stimulates its cleavage activity. EMBO J. 2001;20:5791-801 pubmed
    ..The underlying defect of WS is discussed in light of the evidence for the interaction between WRN and FEN-1. ..
  6. Hasan S, Stucki M, Hassa P, Imhof R, Gehrig P, Hunziker P, et al. Regulation of human flap endonuclease-1 activity by acetylation through the transcriptional coactivator p300. Mol Cell. 2001;7:1221-31 pubmed
    ..p300 formed a complex with flap endonuclease-1 (Fen1) and acetylated Fen1 in vitro...
  7. Shin Y, Amangyeld T, Nguyen T, Munashingha P, Seo Y. Human MUS81 complexes stimulate flap endonuclease 1. FEBS J. 2012;279:2412-30 pubmed publisher
    ..Previously, we reported that Mus81-Mms4 and Rad27 (yeast FEN1, another structure-specific endonuclease) showed mutual stimulation of nuclease activity...
  8. Lv Z, Liu W, Li D, Liu L, Wei J, Zhang J, et al. Association of functional FEN1 genetic variants and haplotypes and breast cancer risk. Gene. 2014;538:42-5 pubmed publisher
    As a tumor suppressor, FEN1 plays an essential role in preventing tumorigenesis...
  9. Jónsson Z, Hindges R, Hubscher U. Regulation of DNA replication and repair proteins through interaction with the front side of proliferating cell nuclear antigen. EMBO J. 1998;17:2412-25 pubmed
    ..in binding to all of the following proteins: DNA polymerase delta, replication factor C, the flap endonuclease Fen1, the cyclin dependent kinase inhibitor p21 and DNA ligase I...
  10. Gary R, Ludwig D, Cornelius H, MacInnes M, Park M. 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. J Biol Chem. 1997;272:24522-9 pubmed
    ..PCNA binds to flap endonuclease 1 (FEN-1), a structure-specific endonuclease involved in DNA replication...
  11. Li X, Li J, Harrington J, Lieber M, Burgers P. Lagging strand DNA synthesis at the eukaryotic replication fork involves binding and stimulation of FEN-1 by proliferating cell nuclear antigen. J Biol Chem. 1995;270:22109-12 pubmed
    ..This interaction is important in the physical orchestration of lagging strand synthesis and may have implications for how PCNA stimulates other members of the FEN-1 nuclease family in a broad range of DNA metabolic transactions. ..
  12. Liu L, Zhou C, Zhou L, Peng L, Li D, Zhang X, et al. Functional FEN1 genetic variants contribute to risk of hepatocellular carcinoma, esophageal cancer, gastric cancer and colorectal cancer. Carcinogenesis. 2012;33:119-23 pubmed publisher
    As a DNA repair protein, Flap endonuclease 1 (FEN1) plays crucial parts in preventing carcinogenesis...
  13. Liu P, Qian L, Sung J, de Souza Pinto N, Zheng L, Bogenhagen D, et al. Removal of oxidative DNA damage via FEN1-dependent long-patch base excision repair in human cell mitochondria. Mol Cell Biol. 2008;28:4975-87 pubmed publisher
    ..in human mitochondrial extracts, and we show that this repair is via long-patch BER (LP-BER) dependent on flap endonuclease 1 (FEN1), not previously known to be present in mitochondria...
  14. Mitra A, Singh N, Singh A, Garg V, Agarwal A, Sharma M, et al. Association of polymorphisms in base excision repair genes with the risk of breast cancer: a case-control study in North Indian women. Oncol Res. 2008;17:127-35 pubmed
    ..rs1130409/T1865G (APEX1), rs1799782/T22142C (XRCC1), rs25487/G23990A (XRCC1), rs4989588/T3337A (FEN1), rs4989586/ G3259A (FEN1), rs4989587/C3315T (FEN1), and rs1050525/G6941T (PCNA) with breast cancer susceptibility...
  15. Zheng L, Zhou M, Guo Z, Lu H, Qian L, Dai H, et al. Human DNA2 is a mitochondrial nuclease/helicase for efficient processing of DNA replication and repair intermediates. Mol Cell. 2008;32:325-36 pubmed publisher
    ..We further demonstrate that hDNA2 and flap endonuclease 1 synergistically process intermediate 5' flap structures occurring in DNA replication and long-patch base ..
  16. Wang W, Bambara R. Human Bloom protein stimulates flap endonuclease 1 activity by resolving DNA secondary structure. J Biol Chem. 2005;280:5391-9 pubmed
    b>Flap endonuclease 1 (FEN1) participates in removal of RNA primers of Okazaki fragments, several DNA repair pathways, and genome stability maintenance...
  17. Sampathi S, Bhusari A, Shen B, Chai W. Human flap endonuclease I is in complex with telomerase and is required for telomerase-mediated telomere maintenance. J Biol Chem. 2009;284:3682-90 pubmed publisher
    ..Here we investigate the role of one of the DNA replication factors, flap endonuclease I (FEN1), in regulating telomerase activity in mammalian cells...
  18. Chen U, Chen S, Saha P, Dutta A. p21Cip1/Waf1 disrupts the recruitment of human Fen1 by proliferating-cell nuclear antigen into the DNA replication complex. Proc Natl Acad Sci U S A. 1996;93:11597-602 pubmed
    Fen1 or maturation factor 1 is a 5'-3' exonuclease essential for the degradation of the RNA primer-DNA junctions at the 5' ends of immature Okazaki fragments prior to their ligation into a continuous DNA strand...
  19. McManus K, Barrett I, Nouhi Y, Hieter P. Specific synthetic lethal killing of RAD54B-deficient human colorectal cancer cells by FEN1 silencing. Proc Natl Acad Sci U S A. 2009;106:3276-81 pubmed publisher
    ..and rad27 mutations in yeast, via knockdown of the highly sequence- and functionally-related proteins RAD54B and FEN1 in a cancer cell line...
  20. Klungland A, Lindahl T. Second pathway for completion of human DNA base excision-repair: reconstitution with purified proteins and requirement for DNase IV (FEN1). EMBO J. 1997;16:3341-8 pubmed
    ..In contrast, the structure-specific nuclease DNase IV (FEN1) was essential for repair of a reduced AP site, which occurred through the long-patch BER pathway...
  21. Guo Z, Kanjanapangka J, Liu N, Liu S, Liu C, Wu Z, et al. Sequential posttranslational modifications program FEN1 degradation during cell-cycle progression. Mol Cell. 2012;47:444-56 pubmed publisher
    We propose that cell-cycle-dependent timing of FEN1 nuclease activity is essential for cell-cycle progression and the maintenance of genome stability...
  22. Hosfield D, Mol C, Shen B, Tainer J. Structure of the DNA repair and replication endonuclease and exonuclease FEN-1: coupling DNA and PCNA binding to FEN-1 activity. Cell. 1998;95:135-46 pubmed
    ..FEN-1 mutations altering PCNA binding should reduce activity during replication, likely causing DNA repeat expansions as seen in some cancers and genetic diseases...
  23. Dianova I, Bohr V, Dianov G. Interaction of human AP endonuclease 1 with flap endonuclease 1 and proliferating cell nuclear antigen involved in long-patch base excision repair. Biochemistry. 2001;40:12639-44 pubmed
    ..We find that human AP endonuclease 1 (APE1) physically interacts with flap endonuclease 1 (FEN1) and with proliferating cell nuclear antigen...
  24. Chen Y, Zhang X, Qiu X, Li J, Yuan Q, Jiang T, et al. Functional FEN1 genetic variants and haplotypes are associated with glioma risk. J Neurooncol. 2013;111:145-51 pubmed publisher
    As a tumor suppressor, FEN1 plays an essential role in keeping genomic instability and preventing tumorigenesis...
  25. Harrington J, Lieber M. The characterization of a mammalian DNA structure-specific endonuclease. EMBO J. 1994;13:1235-46 pubmed
    ..The endo- and exonuclease activities of FEN-1 are discussed in the context of DNA replication, recombination and repair. ..
  26. Friedrich Heineken E, Henneke G, Ferrari E, Hubscher U. The acetylatable lysines of human Fen1 are important for endo- and exonuclease activities. J Mol Biol. 2003;328:73-84 pubmed
    Human Fen1 can be acetylated in vivo and in vitro resulting in reduced endonuclease and exonuclease activities in vitro. Acetylation occurs at four lysines located at the C terminus of Fen1, which is important for DNA binding...
  27. Wu X, Li J, Li X, Hsieh C, Burgers P, Lieber M. Processing of branched DNA intermediates by a complex of human FEN-1 and PCNA. Nucleic Acids Res. 1996;24:2036-43 pubmed
    ..This 42 kDa endo-/exonuclease, FEN-1, is highly homologous to human XP-G, Saccharomyces cerevisiae RAD2 and S.cerevisiae RTH1...
  28. Storici F, Henneke G, Ferrari E, Gordenin D, Hubscher U, Resnick M. The flexible loop of human FEN1 endonuclease is required for flap cleavage during DNA replication and repair. EMBO J. 2002;21:5930-42 pubmed
    The conserved, structure-specific flap endonuclease FEN1 cleaves 5' DNA flaps that arise during replication or repair...
  29. Liu Y, Bambara R. Analysis of human flap endonuclease 1 mutants reveals a mechanism to prevent triplet repeat expansion. J Biol Chem. 2003;278:13728-39 pubmed
    b>Flap endonuclease 1 (FEN1), involved in the joining of Okazaki fragments, has been proposed to restrain DNA repeat sequence expansion, a process associated with aging and disease...
  30. Sharma S, Sommers J, Wu L, Bohr V, Hickson I, Brosh R. Stimulation of flap endonuclease-1 by the Bloom's syndrome protein. J Biol Chem. 2004;279:9847-56 pubmed
    ..We suggest that functional interactions between RecQ helicases and Rad2 family nucleases serve to process DNA substrates that are intermediates in DNA replication and repair.
  31. Qiu J, Liu R, Chapados B, Sherman M, Tainer J, Shen B. Interaction interface of human flap endonuclease-1 with its DNA substrates. J Biol Chem. 2004;279:24394-402 pubmed
    ..R., Hosfield, D. J., Han, S., Qiu, J., Yelent, B., Shen, B., Tainer, J. A. (2004) Cell 116, 39-50) we are able to propose a reasonable model for how the human FEN-1 protein interacts with its DNA substrates. ..
  32. Friedrich Heineken E, Hubscher U. The Fen1 extrahelical 3'-flap pocket is conserved from archaea to human and regulates DNA substrate specificity. Nucleic Acids Res. 2004;32:2520-8 pubmed
    b>Fen1 is a key enzyme for the maintenance of genetic stability in archaea and eukaryotes and is classified as a tumor suppressor...
  33. Sakurai S, Kitano K, Yamaguchi H, Hamada K, Okada K, Fukuda K, et al. Structural basis for recruitment of human flap endonuclease 1 to PCNA. EMBO J. 2005;24:683-93 pubmed
    Flap endonuclease-1 (FEN1) is a key enzyme for maintaining genomic stability and replication. Proliferating cell nuclear antigen (PCNA) binds FEN1 and stimulates its endonuclease activity...
  34. Sharma S, Sommers J, Gary R, Friedrich Heineken E, Hubscher U, Brosh R. The interaction site of Flap Endonuclease-1 with WRN helicase suggests a coordination of WRN and PCNA. Nucleic Acids Res. 2005;33:6769-81 pubmed
    ..protein interaction of WRN and Bloom syndrome (BLM) helicases is with the structure-specific nuclease Flap Endonuclease 1 (FEN-1), an enzyme that is implicated in the processing of DNA intermediates that arise during cellular DNA ..
  35. Liu R, Qiu J, Finger L, Zheng L, Shen B. The DNA-protein interaction modes of FEN-1 with gap substrates and their implication in preventing duplication mutations. Nucleic Acids Res. 2006;34:1772-84 pubmed
    ..Furthermore, based on the evidence that GEN activity in complex with WRN protein cleaves hairpin and internal loop substrates, we suggest that the GEN activity may prevent repeat expansions and duplication mutations. ..
  36. Guo Z, Chavez V, Singh P, Finger L, Hang H, Hegde M, et al. Comprehensive mapping of the C-terminus of flap endonuclease-1 reveals distinct interaction sites for five proteins that represent different DNA replication and repair pathways. J Mol Biol. 2008;377:679-90 pubmed publisher
    ..Replacement of one or more residues with an alanine in many cases leads to the complete loss of interaction, which may consequently lead to severe biological defects in mammals. ..
  37. Kaniak Golik A, Kuberska R, Dzierzbicki P, Sledziewska Gojska E. Activation of Dun1 in response to nuclear DNA instability accounts for the increase in mitochondrial point mutations in Rad27/FEN1 deficient S. cerevisiae. PLoS ONE. 2017;12:e0180153 pubmed publisher
    Rad27/FEN1 nuclease that plays important roles in the maintenance of DNA stability in the nucleus has recently been shown to reside in mitochondria...
  38. Abdel Fatah T, Russell R, Albarakati N, Maloney D, Dorjsuren D, Rueda O, et al. Genomic and protein expression analysis reveals flap endonuclease 1 (FEN1) as a key biomarker in breast and ovarian cancer. Mol Oncol. 2014;8:1326-38 pubmed publisher
    b>FEN1 has key roles in Okazaki fragment maturation during replication, long patch base excision repair, rescue of stalled replication forks, maintenance of telomere stability and apoptosis...
  39. Liu Y, Freeman A, Déclais A, Gartner A, Lilley D. Biochemical and Structural Properties of Fungal Holliday Junction-Resolving Enzymes. Methods Enzymol. 2018;600:543-568 pubmed publisher
    ..GEN1 is an important junction-resolving enzyme in eukaryotic cells, a member of the FEN1/EXO1 superfamily of nucleases...
  40. Li B, Reddy S, Comai L. The Werner Syndrome Helicase Coordinates Sequential Strand Displacement and FEN1-Mediated Flap Cleavage during Polymerase δ Elongation. Mol Cell Biol. 2017;37: pubmed publisher
    ..progression across telomeric G-rich repeats, only WRN promotes sequential strand displacement synthesis and FEN1 cleavage, a critical step in Okazaki fragment maturation, at these sequences...
  41. Sampathi S, Chai W. Mapping the FEN1 interaction domain with hTERT. Biochem Biophys Res Commun. 2011;407:34-8 pubmed publisher
    ..Previously we have demonstrated that the multifunctional DNA replication and repair protein flap endonuclease 1 (FEN1) is in complex with telomerase and may regulate telomerase activity in mammalian cells...
  42. Kwiatkowski D, Czarny P, Toma M, Korycińska A, Sowinska K, Galecki P, et al. Association between Single-Nucleotide Polymorphisms of the hOGG1,NEIL1,APEX1, FEN1,LIG1, and LIG3 Genes and Alzheimer's Disease Risk. Neuropsychobiology. 2016;73:98-107 pubmed publisher
    ..50C>T and c.*83A>C of LIG3, c.977C>G of OGG1, c.*283C>G of NEIL1, c.-441G>A of FEN1, and c.-7C>T of LIG1. We showed that the LIG1 c.-7C>T A/A and LIG3 c...
  43. Kim C, Shin J, Jung S, Park B, Cha H, Park N. Mutational analysis of FEN1 gene in hepatocellular carcinomas. APMIS. 2014;122:663-5 pubmed publisher
  44. PATEL N, Exell J, Jardine E, Ombler B, Finger L, Ciani B, et al. Proline scanning mutagenesis reveals a role for the flap endonuclease-1 helical cap in substrate unpairing. J Biol Chem. 2013;288:34239-48 pubmed publisher
    The prototypical 5'-nuclease, flap endonuclease-1 (FEN1), catalyzes the essential removal of single-stranded flaps during DNA replication and repair. FEN1 hydrolyzes a specific phosphodiester bond one nucleotide into double-stranded DNA...
  45. Heider M, Burkhart B, Santangelo T, Gardner A. Defining the RNaseH2 enzyme-initiated ribonucleotide excision repair pathway in Archaea. J Biol Chem. 2017;292:8835-8845 pubmed publisher
    ..We found that following RNaseH2 cleavage, the combined activities of polymerase B (PolB), flap endonuclease (Fen1), and DNA ligase are required to complete ribonucleotide processing...
  46. Stohr H, Marquardt A, Rivera A, Cooper P, Nowak N, Shows T, et al. A gene map of the Best's vitelliform macular dystrophy region in chromosome 11q12-q13.1. Genome Res. 1998;8:48-56 pubmed
    ..obtained by EST mapping and/or cDNA selection and five genes mapped previously to the interval (CD5, PGA, DDB1, FEN1, and FTH1). Northern blot analyses were performed to determine the expression profiles in various human tissues...
  47. Kathera C, Zhang J, Janardhan A, Sun H, Ali W, Zhou X, et al. Interacting partners of FEN1 and its role in the development of anticancer therapeutics. Oncotarget. 2017;8:27593-27602 pubmed publisher
    ..These interactions used to develop network based biomarkers for early diagnosis of cancer. FEN1(Flap endonuclease 1) is a central component in cellular metabolism, over expression and decrease of FEN1 levels may cause ..
  48. Liu Y, Prasad R, Beard W, Hou E, Horton J, McMurray C, et al. Coordination between polymerase beta and FEN1 can modulate CAG repeat expansion. J Biol Chem. 2009;284:28352-66 pubmed publisher
    ..Unexpectedly, FEN1 promotes expansion by facilitating ligation of hairpins formed by strand slippage...
  49. Cheng I, Chen B, Shuai H, Chien F, Chen P, Hsieh T. Wuho Is a New Member in Maintaining Genome Stability through its Interaction with Flap Endonuclease 1. PLoS Biol. 2016;14:e1002349 pubmed publisher
    ..Mice with mWh knockout are early embryonic lethal and display DNA damage. We identify that the flap endonuclease 1 (FEN1) is one of the interacting proteins...
  50. Martínez Sanz E, Del Río A, Barrio C, Murillo J, Maldonado E, Garcillán B, et al. Alteration of medial-edge epithelium cell adhesion in two Tgf-beta3 null mouse strains. Differentiation. 2008;76:417-30 pubmed
    ..of palatal shelves in both wild-type and Tgf-beta3 null mutant palates of two strains of mice (C57/BL/6J (C57), and MF1) that develop cleft palates of different severity...
  51. Gao A, Zhang J, Zhang W. Evolution of RAD- and DIV-Like Genes in Plants. Int J Mol Sci. 2017;18: pubmed publisher
    ..The results show that there are likely three paralogs of RAD-/I-box-like genes, RAD1, RAD2, and RAD3, which originated in the common ancestor of the core eudicots...
  52. Yadav S, Singh P, Sharma P, Iqbal N, Kaur P, Sharma S, et al. Structure and binding studies of proliferating cell nuclear antigen from Leishmania donovani. Biochim Biophys Acta Proteins Proteom. 2017;1865:1395-1405 pubmed publisher
    ..cyclin-dependent kinase inhibitor-1(CKI-1) and Lys-Thr-Gln-Gly-Arg-Leu-Asp-Ser-Phe-Phe-Thr-Val (P2) from flap endonuclease 1 (Fen-1) as well as with two small molecule inhibitors, (S)-4-(4-(2-amino-3-hydroxypropyl)-2, 6-..
  53. Heale J, Ball A, Schmiesing J, Kim J, Kong X, Zhou S, et al. Condensin I interacts with the PARP-1-XRCC1 complex and functions in DNA single-strand break repair. Mol Cell. 2006;21:837-48 pubmed
    ..Damage-specific association of condensin I with the BER factors flap endonuclease 1 (FEN-1) and DNA polymerase delta/epsilon was also observed, suggesting that condensin I is recruited to ..
  54. Kumar R, Höglund L, Zhao C, Forsti A, Snellman E, Hemminki K. Single nucleotide polymorphisms in the XPG gene: determination of role in DNA repair and breast cancer risk. Int J Cancer. 2003;103:671-5 pubmed
    ..33, 95% CI 1.0-1.8) in cases (C-allele 0.29) compared to controls (C-allele 0.24). Combined heterozygote and variant homozygote genotype frequency was also higher in cases than controls (chi(2) 4.79, p = 0.03; OR 1.50, 95%CI 1.04-2.16). ..
  55. Yu P, Huang B, Shen M, Lau C, Chan E, Michel J, et al. p15(PAF), a novel PCNA associated factor with increased expression in tumor tissues. Oncogene. 2001;20:484-9 pubmed
    ..Notably, p15(PAF) expression in several types of tumor tissues was significantly increased, especially in esophageal tumors. Like PCNA, p15(PAF) may possess prognostic significance in a broad array of human cancers. ..
  56. Finger L, PATEL N, Beddows A, Ma L, Exell J, Jardine E, et al. Observation of unpaired substrate DNA in the flap endonuclease-1 active site. Nucleic Acids Res. 2013;41:9839-47 pubmed publisher
    The structure- and strand-specific phosphodiesterase flap endonuclease-1 (FEN1), the prototypical 5'-nuclease, catalyzes the essential removal of 5'-single-stranded flaps during replication and repair...
  57. Tarantino M, Bilotti K, Huang J, Delaney S. Rate-determining Step of Flap Endonuclease 1 (FEN1) Reflects a Kinetic Bias against Long Flaps and Trinucleotide Repeat Sequences. J Biol Chem. 2015;290:21154-62 pubmed publisher
    b>Flap endonuclease 1 (FEN1) is a structure-specific nuclease responsible for removing 5'-flaps formed during Okazaki fragment maturation and long patch base excision repair...
  58. Teasley D, Parajuli S, Nguyen M, Moore H, Alspach E, Lock Y, et al. Flap Endonuclease 1 Limits Telomere Fragility on the Leading Strand. J Biol Chem. 2015;290:15133-45 pubmed publisher
    ..Here, we demonstrate that flap endonuclease 1 (FEN1), a canonical lagging strand DNA replication protein, is required for normal, complete leading strand ..
  59. Tsutakawa S, Tainer J. Double strand binding-single strand incision mechanism for human flap endonuclease: implications for the superfamily. Mech Ageing Dev. 2012;133:195-202 pubmed publisher
    Detailed structural, mutational, and biochemical analyses of human FEN1/DNA complexes have revealed the mechanism for recognition of 5' flaps formed during lagging strand replication and DNA repair...
  60. Liccardi G, Hartley J, Hochhauser D. Importance of EGFR/ERCC1 interaction following radiation-induced DNA damage. Clin Cancer Res. 2014;20:3496-506 pubmed publisher
    ..These data emphasize the importance of understanding the various mechanisms by which EGFR modulates DNA repair to optimize targeted therapy for patients with cancer. ..
  61. Chung L, Onyango D, Guo Z, Jia P, Dai H, Liu S, et al. The FEN1 E359K germline mutation disrupts the FEN1-WRN interaction and FEN1 GEN activity, causing aneuploidy-associated cancers. Oncogene. 2015;34:902-11 pubmed publisher
    Polymorphisms and somatic mutations in Flap Endonuclease 1 (FEN1), an essential enzyme involved in DNA replication and repair, can lead to functional deficiencies of the FEN1 protein and a predisposition to cancer...
  62. Shen B, Nolan J, Sklar L, Park M. Essential amino acids for substrate binding and catalysis of human flap endonuclease 1. J Biol Chem. 1996;271:9173-6 pubmed
    Human flap endonuclease 1 (FEN-1) is a member of the structure-specific endonuclease family and is involved in DNA repair...
  63. Kim I, Hur N, Shin H, Park B, Cheong H, Bae S. Associations of DNase IV polymorphisms with autoantibodies in patients with systemic lupus erythematosus. Rheumatology (Oxford). 2008;47:996-9 pubmed publisher
    The aim of this study was to investigate genetic polymorphisms of DNase IV and their relationship with SLE and various autoantibodies present in SLE patients...
  64. Jaiswal A, Armas M, Izumi T, Strauss P, Narayan S. Adenomatous polyposis coli interacts with flap endonuclease 1 to block its nuclear entry and function. Neoplasia. 2012;14:495-508 pubmed
    ..that adenomatous polyposis coli (APC) blocks the base excision repair (BER) pathway by interacting with 5'-flap endonuclease 1 (Fen1)...
  65. Farina A, Shin J, Kim D, Bermudez V, Kelman Z, Seo Y, et al. Studies with the human cohesin establishment factor, ChlR1. Association of ChlR1 with Ctf18-RFC and Fen1. J Biol Chem. 2008;283:20925-36 pubmed publisher
    ..The interactions between Fen1 and hChlR1 stimulate the flap endonuclease activity of Fen1...