RAD18

Summary

Gene Symbol: RAD18
Description: Rad18p
Species:

Top Publications

  1. ncbi The RAD6 DNA damage tolerance pathway operates uncoupled from the replication fork and is functional beyond S phase
    Georgios I Karras
    Department of Molecular Cell Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany
    Cell 141:255-67. 2010
  2. ncbi Activation of ubiquitin-dependent DNA damage bypass is mediated by replication protein a
    Adelina A Davies
    Cancer Research UK London Research Institute, Clare Hall Laboratories, Blanche Lane, South Mimms EN6 3LD, UK
    Mol Cell 29:625-36. 2008
  3. ncbi Ubiquitylation of the 9-1-1 checkpoint clamp is independent of rad6-rad18 and DNA damage
    Adelina A Davies
    Cancer Research UK London Research Institute, Clare Hall Laboratories, Blanche Lane, South Mimms EN6 3LD, UK
    Cell 141:1080-7. 2010
  4. ncbi Control of spontaneous and damage-induced mutagenesis by SUMO and ubiquitin conjugation
    Philipp Stelter
    Max Planck Institute for Terrestrial Microbiology, Karl von Frisch Strasse, 35043 Marburg, Germany
    Nature 425:188-91. 2003
  5. ncbi Mechanistic analysis of PCNA poly-ubiquitylation by the ubiquitin protein ligases Rad18 and Rad5
    Joanne L Parker
    Clare Hall Laboratories, Cancer Research UK London Research Institute, South Mimms, Herts, UK
    EMBO J 28:3657-66. 2009
  6. ncbi Saccharomyces cerevisiae MGS1 is essential in strains deficient in the RAD6-dependent DNA damage tolerance pathway
    Takashi Hishida
    Department of Molecular Microbiology, Research Institute for Microbial Diseases, Osaka University, Yamadaoka 3 1, Suita, Osaka 565 0871, Japan
    EMBO J 21:2019-29. 2002
  7. ncbi Mgs1 and Rad18/Rad5/Mms2 are required for survival of Saccharomyces cerevisiae mutants with novel temperature/cold sensitive alleles of the DNA polymerase delta subunit, Pol31
    Niloofar Davoodi Vijeh Motlagh
    Molecular Cell Biology Laboratory, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba 6 3, Sendai, Miyagi 980 8578, Japan
    DNA Repair (Amst) 5:1459-74. 2006
  8. ncbi SUMOylation regulates Rad18-mediated template switch
    Dana Branzei
    IFOM, the FIRC Institute for Molecular Oncology Foundation, IFOM IEO Campus, Via Adamello 16, 20139 Milan, Italy
    Nature 456:915-20. 2008
  9. ncbi Regulation of gross chromosomal rearrangements by ubiquitin and SUMO ligases in Saccharomyces cerevisiae
    Akira Motegi
    Genome Instability Section, Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Building 49, Room 4A22, Bethesda, MD 20892, USA
    Mol Cell Biol 26:1424-33. 2006
  10. ncbi The Saccharomyces cerevisiae Rad6 postreplication repair and Siz1/Srs2 homologous recombination-inhibiting pathways process DNA damage that arises in asf1 mutants
    Ellen S Kats
    Ludwig Institute for Cancer Research, Departments of Medicine and Cellular and Molecular Medicine, and Biomedical Sciences Graduate Program, UC San Diego School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093 0669, USA
    Mol Cell Biol 29:5226-37. 2009

Research Grants

Scientific Experts

  • Takashi Hishida
  • Dana Branzei
  • John Game
  • Meng Er Huang
  • H D Ulrich
  • A A Friedl
  • Zhihao Zhuang
  • W Xiao
  • Adelina A Davies
  • Joanne L Parker
  • Diana Huttner
  • Shuhua Chen
  • Hanna Windecker
  • Lindsey J Bostelman
  • Louise Prakash
  • Satya Prakash
  • Akira Motegi
  • Stefan Jentsch
  • Marcelo de Padula
  • Kyungjae Myung
  • Bryan M O'Neill
  • Irene Saugar
  • Floyd E Romesberg
  • Alejandro Chavez
  • Oren Parnas
  • Martin Kupiec
  • Neta Agmon
  • Boris Pfander
  • Batia Liefshitz
  • Georgios I Karras
  • Christopher D Putnam
  • Andrew L Paek
  • Landon Pastushok
  • Richard D Kolodner
  • Carsten Hoege
  • Patricia Auffret van der Kemp
  • Denise Hanway
  • Sierra Colavito
  • Ellen S Kats
  • Jun Huang
  • Cyrille Le Breton
  • Ewa T Lis
  • Margery L Evans
  • María Victoria Vázquez
  • V Bailly
  • Yu Fu
  • Jeffrey S Thompson
  • Ashley M Albrecht
  • Andrew M Keller
  • Sergio R Santa Maria
  • Patrick Sung
  • Konstantinos Kiakos
  • Danielle L Daee
  • Lumir Krejci
  • Serge Boiteux
  • Francis Fabre
  • Kristina Herzberg
  • Justyna McIntyre
  • Clark C Chen
  • Balazs Ribar
  • Niloofar Davoodi Vijeh Motlagh
  • Lajos Haracska
  • Stephanie Smith
  • Hengshan Zhang
  • Efterpi Papouli
  • Brenda K Minesinger
  • Ji Young Hwang
  • Jodie K Chin
  • Christine Soustelle
  • Sue Jinks-Robertson
  • George-Lucian Moldovan
  • George Lucian Moldovan
  • Philipp Stelter
  • Elizabeth A Winzeler
  • Adam Wood
  • Natalie J Morey
  • Stacey Broomfield
  • Shengkai Zhao
  • F Brad Johnson
  • Moran Yovel
  • Adi Zipin-Roitman
  • Rona Amishay
  • Yaniv Harari
  • Vishesh Agrawal
  • Tikvah K Hayes
  • Andrea Neiss
  • Ted Weinert
  • Salma Kaochar
  • Michelle Hanna
  • Hope Jones

Detail Information

Publications79

  1. ncbi The RAD6 DNA damage tolerance pathway operates uncoupled from the replication fork and is functional beyond S phase
    Georgios I Karras
    Department of Molecular Cell Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany
    Cell 141:255-67. 2010
    ..We therefore propose that the RAD6 pathway acts on single-stranded gaps left behind newly restarted replication forks...
  2. ncbi Activation of ubiquitin-dependent DNA damage bypass is mediated by replication protein a
    Adelina A Davies
    Cancer Research UK London Research Institute, Clare Hall Laboratories, Blanche Lane, South Mimms EN6 3LD, UK
    Mol Cell 29:625-36. 2008
    ..We found that RPA directly interacts with the ubiquitin ligase responsible for the modification of PCNA, Rad18, both in yeast and in mammalian cells...
  3. ncbi Ubiquitylation of the 9-1-1 checkpoint clamp is independent of rad6-rad18 and DNA damage
    Adelina A Davies
    Cancer Research UK London Research Institute, Clare Hall Laboratories, Blanche Lane, South Mimms EN6 3LD, UK
    Cell 141:1080-7. 2010
    A recent report proposed a function of the ubiquitin conjugation factors Rad6 and Rad18 comparable to the bacterial SOS response, controlling damage-induced transcriptional activation and contributing to checkpoint signaling...
  4. ncbi Control of spontaneous and damage-induced mutagenesis by SUMO and ubiquitin conjugation
    Philipp Stelter
    Max Planck Institute for Terrestrial Microbiology, Karl von Frisch Strasse, 35043 Marburg, Germany
    Nature 425:188-91. 2003
    ..Our findings assign a function to SUMO during S phase and demonstrate how ubiquitin and SUMO, by regulating the accuracy of replication and repair, contribute to overall genomic stability...
  5. ncbi Mechanistic analysis of PCNA poly-ubiquitylation by the ubiquitin protein ligases Rad18 and Rad5
    Joanne L Parker
    Clare Hall Laboratories, Cancer Research UK London Research Institute, South Mimms, Herts, UK
    EMBO J 28:3657-66. 2009
    ..analysed the mechanism of poly-ubiquitylation of the replication clamp PCNA by two cooperating E2-E3 pairs, Rad6-Rad18 and Ubc13-Mms2-Rad5...
  6. ncbi Saccharomyces cerevisiae MGS1 is essential in strains deficient in the RAD6-dependent DNA damage tolerance pathway
    Takashi Hishida
    Department of Molecular Microbiology, Research Institute for Microbial Diseases, Osaka University, Yamadaoka 3 1, Suita, Osaka 565 0871, Japan
    EMBO J 21:2019-29. 2002
    ..We found that mgs1 is synthetic lethal with rad6 and exhibits a synergistic growth defect with rad18 and rad5, which are members of the RAD6 epistasis group important for tolerance of DNA damage during DNA ..
  7. ncbi Mgs1 and Rad18/Rad5/Mms2 are required for survival of Saccharomyces cerevisiae mutants with novel temperature/cold sensitive alleles of the DNA polymerase delta subunit, Pol31
    Niloofar Davoodi Vijeh Motlagh
    Molecular Cell Biology Laboratory, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba 6 3, Sendai, Miyagi 980 8578, Japan
    DNA Repair (Amst) 5:1459-74. 2006
    ..Surprisingly, deletions of RAD18 and MGS1 aggravated the temperature sensitivity conferred by most ts or cs alleles and specifically suppressed the ..
  8. ncbi SUMOylation regulates Rad18-mediated template switch
    Dana Branzei
    IFOM, the FIRC Institute for Molecular Oncology Foundation, IFOM IEO Campus, Via Adamello 16, 20139 Milan, Italy
    Nature 456:915-20. 2008
    ..Gap-filling repair requires homologous recombination as well as Rad18- and Rad5-mediated proliferating cell nuclear antigen (PCNA) polyubiquitylation...
  9. ncbi Regulation of gross chromosomal rearrangements by ubiquitin and SUMO ligases in Saccharomyces cerevisiae
    Akira Motegi
    Genome Instability Section, Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Building 49, Room 4A22, Bethesda, MD 20892, USA
    Mol Cell Biol 26:1424-33. 2006
    ..Previously, we showed that inactivation of Rad5 or Rad18, ubiquitin ligases (E3) targeting for proliferating cell nuclear antigen (PCNA), increases the de novo telomere ..
  10. ncbi The Saccharomyces cerevisiae Rad6 postreplication repair and Siz1/Srs2 homologous recombination-inhibiting pathways process DNA damage that arises in asf1 mutants
    Ellen S Kats
    Ludwig Institute for Cancer Research, Departments of Medicine and Cellular and Molecular Medicine, and Biomedical Sciences Graduate Program, UC San Diego School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093 0669, USA
    Mol Cell Biol 29:5226-37. 2009
    ..Our results show that ASF1 probably contributes to the maintenance of genome stability through multiple mechanisms, some of which involve the PRR and HRS pathways...
  11. ncbi RAD6-dependent DNA repair is linked to modification of PCNA by ubiquitin and SUMO
    Carsten Hoege
    Department of Molecular Cell Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18a, 82152 Martinsried, Germany
    Nature 419:135-41. 2002
    ..enzymes RAD6 and the MMS2-UBC13 heterodimer, which are recruited to chromatin by the RING-finger proteins RAD18 and RAD5, respectively...
  12. ncbi The post-replication repair RAD18 and RAD6 genes are involved in the prevention of spontaneous mutations caused by 7,8-dihydro-8-oxoguanine in Saccharomyces cerevisiae
    Marcelo de Padula
    CEA, Departement de Radiobiologie et Radiopathologie, UMR217 CNRS Radiobiologie Moléculaire et Cellulaire, BP6, 92265 Fontenay aux Roses, France
    Nucleic Acids Res 32:5003-10. 2004
    ..In the present study, we show the RAD18 and RAD6 genes that are required to initiate post-replication repair (PRR) are also involved in the prevention of ..
  13. ncbi SUMO modification of PCNA is controlled by DNA
    Joanne L Parker
    Cancer Research UK London Research Institute, Clare Hall Laboratories, South Mimms, UK
    EMBO J 27:2422-31. 2008
    ..Instead, the stimulatory effect of DNA on conjugation is mainly attributable to DNA binding of PCNA itself. These findings imply a change in the properties of PCNA upon loading that enhances its capacity to be sumoylated...
  14. ncbi Genetic analysis of ionizing radiation-induced mutagenesis in Saccharomyces cerevisiae reveals TransLesion Synthesis (TLS) independent of PCNA K164 SUMOylation and ubiquitination
    Clark C Chen
    Department of Neurosurgery, Massachusetts General Hospital, 55 Fruit St, Boston, MA 02114, USA
    DNA Repair (Amst) 5:1475-88. 2006
    ..Further analysis of a mutant simultaneously defective in SUMOylation and mono-ubiquitination (rad18 siz1) revealed that these modifications redundantly affected TLS as well as NHEJ...
  15. ncbi Functional and physical interaction of yeast Mgs1 with PCNA: impact on RAD6-dependent DNA damage tolerance
    Takashi Hishida
    Genome Dynamics Group, Research Institute for Microbial Diseases, Osaka University, Yamadaoka 3 1, Suita, Osaka 565 0871, Japan
    Mol Cell Biol 26:5509-17. 2006
    ..We also show that PCNA sumoylation inhibits the growth of mgs1 rad18 double mutants, in which PCNA sumoylation and the Srs2 DNA helicase coordinately prevent RAD52-dependent ..
  16. ncbi Architecture and assembly of poly-SUMO chains on PCNA in Saccharomyces cerevisiae
    Hanna Windecker
    Cancer Research UK London Research Institute, Clare Hall Laboratories, Blanche Lane, South Mimms EN6 3LD, UK
    J Mol Biol 376:221-31. 2008
    ....
  17. ncbi Crosstalk between SUMO and ubiquitin on PCNA is mediated by recruitment of the helicase Srs2p
    Efterpi Papouli
    Cancer Research UK, Clare Hall Laboratories, Blanche Lane, South Mimms, Herts EN6 3LD, United Kingdom
    Mol Cell 19:123-33. 2005
    ..Our findings suggest a mechanism by which SUMO and ubiquitin cooperatively control the choice of pathway for the processing of DNA lesions during replication...
  18. ncbi Ubiquitylation of yeast proliferating cell nuclear antigen and its implications for translesion DNA synthesis
    Lajos Haracska
    Institute of Genetics, Biological Research Center, Hungarian Academy of Sciences, H 6701 Szeged, Hungary
    Proc Natl Acad Sci U S A 103:6477-82. 2006
    The Rad6-Rad18 ubiquitin-conjugating enzyme complex promotes replication through DNA lesions by means of at least three different pathways: the DNA polymerase (Pol) eta- and zeta-dependent translesion DNA synthesis (TLS) and a Rad5-Mms2-..
  19. ncbi The RING finger ATPase Rad5p of Saccharomyces cerevisiae contributes to DNA double-strand break repair in a ubiquitin-independent manner
    Shuhua Chen
    Max Planck Institute for Terrestrial Microbiology, Karl von Frisch Strasse D 35043, Marburg, Germany
    Nucleic Acids Res 33:5878-86. 2005
    ....
  20. ncbi Rad6-Rad18 mediates a eukaryotic SOS response by ubiquitinating the 9-1-1 checkpoint clamp
    Yu Fu
    Department of Microbiology and Immunology, University of Saskatchewan, Saskatoon, SK, S7N 5E5, Canada
    Cell 133:601-11. 2008
    ..Here, we demonstrate that the ubiquitination complex Rad6-Rad18 is required for the increased transcription of a large number of yeast genes in response to DNA damage...
  21. ncbi Srs2 removes deadly recombination intermediates independently of its interaction with SUMO-modified PCNA
    Cyrille Le Breton
    CEA DSV Institut de Radiobiologie Cellulaire et Moléculaire, UMR217 CNRS CEA, F 92265 Fontenay aux Roses, France
    Nucleic Acids Res 36:4964-74. 2008
    ..In addition, crossover (CO) frequencies are increased in both mutants. The different roles of Srs2, in relation to its eventual recruitment by sumoylated PCNA, are discussed...
  22. ncbi Postreplication repair inhibits CAG.CTG repeat expansions in Saccharomyces cerevisiae
    Danielle L Daee
    Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198, USA
    Mol Cell Biol 27:102-10. 2007
    ..Like srs2 mutants, expansions are elevated in rad18 and rad5 mutants, as well as the PRR-specific PCNA alleles pol30-K164R and pol30-K127/164R...
  23. ncbi Analysis of mitotic and meiotic defects in Saccharomyces cerevisiae SRS2 DNA helicase mutants
    F Palladino
    Department of Biochemistry and Kaplan Cancer Center, New York University Medical Center, New York 10016
    Genetics 132:23-37. 1992
    ..of the SRS2 DNA helicase gene of Saccharomyces cerevisiae has been reported to suppress the UV sensitivity of rad18 mutants. New alleles of SRS2 were recovered using this suppressor phenotype...
  24. ncbi Yeast DNA repair proteins Rad6 and Rad18 form a heterodimer that has ubiquitin conjugating, DNA binding, and ATP hydrolytic activities
    V Bailly
    Sealy Center for Molecular Science, University of Texas Medical Branch, Galveston, Texas 77555 1061, USA
    J Biol Chem 272:23360-5. 1997
    The RAD6 and RAD18 genes of Saccharomyces cerevisiae are required for postreplicative bypass of ultraviolet (UV)-damaged DNA and for UV mutagenesis...
  25. ncbi The Saccharomyces cerevisiae RAD30 gene, a homologue of Escherichia coli dinB and umuC, is DNA damage inducible and functions in a novel error-free postreplication repair mechanism
    J P McDonald
    Section on DNA Replication, Repair and Mutagenesis, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892 2725, USA
    Genetics 147:1557-68. 1997
    ..However, unlike rev mutants, no defect in UV-induced reversion was seen in rad30 strains. While rad6 and rad18 are both epistatic to rad30, no epistasis was observed with rev1, rev3, rev7 or rad5, all of which are members of ..
  26. ncbi Specific complex formation between yeast RAD6 and RAD18 proteins: a potential mechanism for targeting RAD6 ubiquitin-conjugating activity to DNA damage sites
    V Bailly
    Department of Biophysics, University of Rochester, New York 14642
    Genes Dev 8:811-20. 1994
    ..Here, we show that RAD6 forms a specific complex with the product of the DNA repair gene RAD18. The biological significance of this interaction is attested by the observation that overproduction of the rad6 ..
  27. ncbi MMS2, encoding a ubiquitin-conjugating-enzyme-like protein, is a member of the yeast error-free postreplication repair pathway
    S Broomfield
    Department of Microbiology, University of Saskatchewan, 107 Wiggins Road, Saskatoon, SK Canada S7N 5E5
    Proc Natl Acad Sci U S A 95:5678-83. 1998
    ..The rad6 and rad18 mutants are defective in both pathways, and the rev3 mutant affects only the mutagenesis pathway, but a yeast gene ..
  28. ncbi Two RING finger proteins mediate cooperation between ubiquitin-conjugating enzymes in DNA repair
    H D Ulrich
    Department of Molecular Cell Biology, Max Planck Institute for Biochemistry, Am Klopferspitz 18a, 82152 Martinsried, Germany
    EMBO J 19:3388-97. 2000
    ..We show that two chromatin-associated RING finger proteins, RAD18 and RAD5, play a central role in mediating physical contacts between the members of the RAD6 pathway...
  29. ncbi Deletion of the SRS2 gene suppresses elevated recombination and DNA damage sensitivity in rad5 and rad18 mutants of Saccharomyces cerevisiae
    A A Friedl
    Institute of Radiation Biology, GSF National Research Center for Environment and Health, P O Box 1149, 85758, Oberschleissheim, Germany
    Mutat Res 486:137-46. 2001
    The Saccharomyces cerevisiae genes RAD5, RAD18, and SRS2 are proposed to act in post-replicational repair of DNA damage...
  30. ncbi Suppression of a new allele of the yeast RAD52 gene by overexpression of RAD51, mutations in srs2 and ccr4, or mating-type heterozygosity
    D Schild
    Life Sciences Division, Lawrence Berkeley Laboratory, California 94720, USA
    Genetics 140:115-27. 1995
    ..rad52-20) is partially suppressed by an srs2 deletion; srs2 mutations normally act to suppress only rad6 and rad18 mutations...
  31. ncbi The srs2 suppressor of UV sensitivity acts specifically on the RAD5- and MMS2-dependent branch of the RAD6 pathway
    H D Ulrich
    Max Planck Institute for Terrestrial Microbiology, Karl von Frisch Strasse, D 35043 Marburg, Germany
    Nucleic Acids Res 29:3487-94. 2001
    ..Loss-of-function mutations in srs2 suppress the extreme sensitivity towards UV radiation of rad6 and rad18 mutants, both of which are impaired in post-replication DNA repair and damage-induced mutagenesis...
  32. ncbi The hyper-gene conversion hpr5-1 mutation of Saccharomyces cerevisiae is an allele of the SRS2/RADH gene
    L Rong
    Department of Biochemistry, New York University Medical Center, New York 10016
    Genetics 127:75-85. 1991
    ..This mutation suppresses the UV sensitive phenotype of rad18 mutations in hpr5-1 rad18 double mutants by channeling the aborted repair events into a recombination repair ..
  33. ncbi The error-free component of the RAD6/RAD18 DNA damage tolerance pathway of budding yeast employs sister-strand recombination
    Hengshan Zhang
    Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA
    Proc Natl Acad Sci U S A 102:15954-9. 2005
    ..We have investigated this mechanism in Saccharomyces cerevisiae, in which it is the major component of the RAD6/RAD18 pathway, by transforming an isogenic set of rad1Delta excision-defective strains with plasmids that carry a single ..
  34. ncbi The repair of DNA methylation damage in Saccharomyces cerevisiae
    W Xiao
    Department of Microbiology, University of Saskatchewan, Saskatoon, SK, S7N 5E5, Canada
    Curr Genet 30:461-8. 1996
    ..We found that cells carrying rad6, rad18, rad50 and rad52 single mutations are far more sensitive to killing by MMS than the mag1 mutant, that double ..
  35. ncbi Pol32, a subunit of Saccharomyces cerevisiae DNA polymerase delta, suppresses genomic deletions and is involved in the mutagenic bypass pathway
    Meng Er Huang
    UMR6061 CNRS, Genetique et Developpement, Faculte de Medecine, 35043 Rennes, France
    Genetics 160:1409-22. 2002
    ..Taken together, these observations indicate that Pol32 is important in ensuring genome stability and in mutagenesis...
  36. ncbi SUMO-modified PCNA recruits Srs2 to prevent recombination during S phase
    Boris Pfander
    Department of Molecular Cell Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany
    Nature 436:428-33. 2005
    ..Our finding suggests a model in which SUMO-modified PCNA recruits Srs2 in S phase in order to prevent unwanted recombination events of replicating chromosomes...
  37. ncbi The product of Saccharomyces cerevisiae WHIP/MGS1, a gene related to replication factor C genes, interacts functionally with DNA polymerase delta
    D Branzei
    Molecular Cell Biology Laboratory, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, 980 8578, Japan
    Mol Genet Genomics 268:371-86. 2002
    ..Possible roles of Mgs1, DNA polymerase delta, Rad18 and Mms2 in replication and replication fork restart are discussed.
  38. ncbi Requirement of Nse1, a subunit of the Smc5-Smc6 complex, for Rad52-dependent postreplication repair of UV-damaged DNA in Saccharomyces cerevisiae
    Sergio R Santa Maria
    Department of Biochemistry and Molecular Biology, University of Texas Medical Branch at Galveston, 301 University Blvd, Galveston, TX 77555 1061, USA
    Mol Cell Biol 27:8409-18. 2007
    In Saccharomyces cerevisiae, postreplication repair (PRR) of UV-damaged DNA occurs by a Rad6-Rad18- and an Mms2-Ubc13-Rad5-dependent pathway or by a Rad52-dependent pathway...
  39. ncbi The genome maintenance factor Mgs1 is targeted to sites of replication stress by ubiquitylated PCNA
    Irene Saugar
    Cancer Research UK London Research Institute, Clare Hall Laboratories, Blanche Lane, South Mimms, EN6 3LD, UK
    Nucleic Acids Res 40:245-57. 2012
    ..Our identification of Mgs1 as a UBZ-dependent downstream effector of ubiquitylated PCNA suggests an explanation for the ambivalent role of the protein in damage processing...
  40. ncbi Elg1, the major subunit of an alternative RFC complex, interacts with SUMO-processing proteins
    Oren Parnas
    Department of Molecular Microbiology and Biotechnology, Tel Aviv University, Ramat Aviv, Israel
    Cell Cycle 10:2894-903. 2011
    ..Thus our results highlight the many important roles played by Elg1, some of which are PCNA-dependent and some PCNA-independent...
  41. ncbi 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...
  42. ncbi Homologous recombination-dependent rescue of deficiency in the structural maintenance of chromosomes (Smc) 5/6 complex
    Alejandro Chavez
    Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 286:5119-25. 2011
    ..These data as a whole highlight a role for Smc5/6 and Sgs1 in the resolution of Mph1-dependent HR intermediates...
  43. ncbi Functional significance of the Rad51-Srs2 complex in Rad51 presynaptic filament disruption
    Sierra Colavito
    Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06520, USA
    Nucleic Acids Res 37:6754-64. 2009
    ..These results highlight the importance of Rad51 interaction in the anti-recombinase function of Srs2, and provide evidence that this Srs2 function can be uncoupled from its helicase activity...
  44. ncbi Regulation of polymerase exchange between Poleta and Poldelta by monoubiquitination of PCNA and the movement of DNA polymerase holoenzyme
    Zhihao Zhuang
    Department of Chemistry, 414 Wartik Laboratory, Pennsylvania State University, University Park, PA 16802, USA
    Proc Natl Acad Sci U S A 105:5361-6. 2008
    ..Thus the removal of the ubiquitin moiety from PCNA is likely required for the reverse exchange step after the lesion bypass synthesis by Poleta...
  45. ncbi RAD18 transmits DNA damage signalling to elicit homologous recombination repair
    Jun Huang
    Department of Therapeutic Radiology, Yale University School of Medicine, P O Box 208040, New Haven, CT 06520, USA
    Nat Cell Biol 11:592-603. 2009
    ..Here we describe a new role for the E3 ligase RAD18 as the integral component in translating the damage response signal to orchestrate homologous recombination repair ..
  46. ncbi Post-replication repair suppresses duplication-mediated genome instability
    Christopher D Putnam
    Ludwig Institute for Cancer Research, University of California San Diego School of Medicine, La Jolla, California, United States of America
    PLoS Genet 6:e1000933. 2010
    ..Here, we found that the RAD6- and RAD18-dependent post-replication repair (PRR) and the RAD5-, MMS2-, UBC13-dependent error-free PRR branch acted in ..
  47. ncbi Srs2 plays a critical role in reversible G2 arrest upon chronic and low doses of UV irradiation via two distinct homologous recombination-dependent mechanisms in postreplication repair-deficient cells
    Takashi Hishida
    Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan
    Mol Cell Biol 30:4840-50. 2010
    ..The first (required to suppress HR during PRR) is regulated by PCNA sumoylation, whereas the second (required for HR-dependent recovery following CLUV exposure) is regulated by CDK1-dependent phosphorylation...
  48. ncbi The role of replication bypass pathways in dicentric chromosome formation in budding yeast
    Andrew L Paek
    Department of Molecular and Cellular Biology, University of Arizona, Tucson, Arizona 85721, USA
    Genetics 186:1161-73. 2010
    ..Fourth, by studying genes implicated in suppression of GCRs in other studies, we found that inverted repeat fusion has a profile of genetic regulation distinct from these other major forms of GCR formation...
  49. ncbi The Rad1-Rad10 complex promotes the production of gross chromosomal rearrangements from spontaneous DNA damage in Saccharomyces cerevisiae
    Ji Young Hwang
    Genome Instability Section, Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Genetics 169:1927-37. 2005
    ..Results presented here suggest that Rad1-Rad10 functions at different stages of GCR formation and that there is an alternative pathway for the GCR formation that is independent of Rad1-Rad10...
  50. ncbi A new Saccharomyces cerevisiae strain with a mutant Smt3-deconjugating Ulp1 protein is affected in DNA replication and requires Srs2 and homologous recombination for its viability
    Christine Soustelle
    Commissaritat à l Energy Atomique, UMR 217 CNRS CEA, DSV DRR, Fontenay aux Roses, France
    Mol Cell Biol 24:5130-43. 2004
    ..These structures are believed to generate different recombination intermediates. Some of them are fixed by recombination, and others require Srs2 to be reversed and fixed by an alternate pathway...
  51. ncbi Delineating the requirements for spontaneous DNA damage resistance pathways in genome maintenance and viability in Saccharomyces cerevisiae
    Natalie J Morey
    Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia 30322, USA
    Genetics 164:443-55. 2003
    ..In diploids, the presence of PRR alone may confer a lethal mutation load or, alternatively, PRR alone may be insufficient to deal with potentially lethal, replication-blocking lesions...
  52. ncbi Bre1, an E3 ubiquitin ligase required for recruitment and substrate selection of Rad6 at a promoter
    Adam Wood
    Department of Biochemistry, Saint Louis University School of Medicine, 1402 South Grand Boulevard, St Louis, MO 63104, USA
    Mol Cell 11:267-74. 2003
    ..These results suggest that Bre1 is the likely E3 enzyme that directs Rad6 to modify chromatin and ultimately to affect gene expression...
  53. ncbi Roles of RAD6 epistasis group members in spontaneous polzeta-dependent translesion synthesis in Saccharomyces cerevisiae
    Brenda K Minesinger
    Biochemistry, Cell and Developmental Biology Program of the Graduate Division of Biological and Biomedical Sciences, Emory University, Atlanta, GA 30322, USA
    Genetics 169:1939-55. 2005
    ..data are consistent with a model in which Polzeta-dependent mutagenesis relies on the presence of either Rad5 or Rad18, which promote two distinct error-prone pathways that partially overlap with respect to lesion specificity...
  54. ncbi Previously uncharacterized genes in the UV- and MMS-induced DNA damage response in yeast
    Denise Hanway
    Department of Chemistry and Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 99:10605-10. 2002
    ..Epistatsis analysis of four of the genes was performed to determine the DNA damage repair pathways in which the protein products function...
  55. ncbi Involvement of the yeast DNA polymerase delta in DNA repair in vivo
    L Giot
    Institut Curie Biologie, Centre Universitaire, Orsay, France
    Genetics 146:1239-51. 1997
    ..SDP5 is most probably the p55 subunit of Pol delta of S. cerevisiae and seems to be associated with the catalytic subunit for both DNA replication and DNA repair...
  56. ncbi Coordinated functions of WSS1, PSY2 and TOF1 in the DNA damage response
    Bryan M O'Neill
    Department of Chemistry, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, CA 92037, USA
    Nucleic Acids Res 32:6519-30. 2004
    ..Tof1 is known to be involved in stabilizing stalled replication forks and our data suggest that Wss1 and Psy2 similarly function to stabilize or process stalled or collapsed replication forks...
  57. ncbi Requirement of ELC1 for RNA polymerase II polyubiquitylation and degradation in response to DNA damage in Saccharomyces cerevisiae
    Balazs Ribar
    Sealy Center for Molecular Science, University of Texas Medical Branch at Galveston, Galveston, TX 77555 1061, USA
    Mol Cell Biol 26:3999-4005. 2006
    ....
  58. ncbi Constitutive fusion of ubiquitin to PCNA provides DNA damage tolerance independent of translesion polymerase activities
    Landon Pastushok
    Department of Microbiology and Immunology, University of Saskatchewan, Saskatoon, SK, Canada
    Nucleic Acids Res 38:5047-58. 2010
    ..As expected, the DNA damage resistance provided by PCNA.Ub is not dependent on RAD18 or UBC13. Surprisingly, inactivation of TLS polymerases did not abolish PCNA...
  59. ncbi The RAD6/BRE1 histone modification pathway in Saccharomyces confers radiation resistance through a RAD51-dependent process that is independent of RAD18
    John C Game
    Life Sciences Division, Lawrence Berkeley National Laboratory, CA 94720, USA
    Genetics 173:1951-68. 2006
    ..We conclude that IR resistance conferred by BRE1 and DOT1 is mediated through homologous recombinational repair, not postreplication repair, and confirm findings of a G1 checkpoint role for the RAD6/BRE1/DOT1 pathway...
  60. ncbi Phosphorylation of Rad55 on serines 2, 8, and 14 is required for efficient homologous recombination in the recovery of stalled replication forks
    Kristina Herzberg
    Section of Microbiology, University of California, Davis, Davis, CA 95616 8665, USA
    Mol Cell Biol 26:8396-409. 2006
    ..These results suggest that Rad55-S2,8,14 phosphorylation activates recombinational repair, allowing for faster recovery after genotoxic stress...
  61. ncbi Meiotic recombination and sporulation in repair-deficient strains of yeast
    E L Dowling
    Genetics 109:283-302. 1985
    ..rad1, rad2, rad3, rad4, rad10, rad14 and rad16), and three were defective in mutagenic repair (rad5, rad9 and rad18)...
  62. ncbi Rad18/Rad5/Mms2-mediated polyubiquitination of PCNA is implicated in replication completion during replication stress
    Dana Branzei
    Molecular Cell Biology Laboratory, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, 980 8578, Japan
    Genes Cells 9:1031-42. 2004
    ..mutants hys2-1 and cdc2-1 as well as the synthetic lethality of cdc2-1 pol32delta mutants, suggesting a role for Rad18 in modulating DNA replication...
  63. ncbi The Saccharomyces cerevisiae RAD9, RAD17, RAD24 and MEC3 genes are required for tolerating irreparable, ultraviolet-induced DNA damage
    A G Paulovich
    Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA
    Genetics 150:75-93. 1998
    ..Therefore, checkpoint genes not only control cell cycle progression in response to damage, but also play a role in accommodating DNA damage during replication...
  64. ncbi Domains required for dimerization of yeast Rad6 ubiquitin-conjugating enzyme and Rad18 DNA binding protein
    V Bailly
    Sealy Center for Molecular Science, University of Texas Medical Branch, Galveston 77555 1061, USA
    Mol Cell Biol 17:4536-43. 1997
    ..Rad6 mediates its DNA repair role via its association with Rad18, whose DNA binding activity may target the Rad6-Rad18 complex to damaged sites in DNA...
  65. ncbi Characterization of postreplication repair in Saccharomyces cerevisiae and effects of rad6, rad18, rev3 and rad52 mutations
    L Prakash
    Mol Gen Genet 184:471-8. 1981
    ..The rad6 mutant does not carry out postreplication repair, the rad18 and rad52 mutants show great inhibition while the rev3 mutation does not affect postreplication repair...
  66. ncbi PCNA monoubiquitylation and DNA polymerase eta ubiquitin-binding domain are required to prevent 8-oxoguanine-induced mutagenesis in Saccharomyces cerevisiae
    Patricia Auffret van der Kemp
    CEA, IRCM, UMR217 CNRS Radiobiologie Moléculaire et Cellulaire, 18 route du Panorama, BP6, 92265 Fontenay aux Roses, France
    Nucleic Acids Res 37:2549-59. 2009
    ..Here, we present evidence for cooperation between Rad18-Rad6-dependent monoubiquitylation of PCNA at K164, the damage-tolerant DNA polymerase eta and the mismatch repair ..
  67. ncbi Methylation of histone H3 lysine-79 by Dot1p plays multiple roles in the response to UV damage in Saccharomyces cerevisiae
    Lindsey J Bostelman
    Department of Biology, Denison University, 213 Talbot Hall, Granville, Ohio 43023, USA
    DNA Repair (Amst) 6:383-95. 2007
    ..The overall results indicate the existence of distinct and separable roles of histone H3 lysine-79 methylation in the response to UV damage, potentially serving to coordinate the various repair processes...
  68. ncbi DNA sequence selective adenine alkylation, mechanism of adduct repair, and in vivo antitumor activity of the novel achiral seco-amino-cyclopropylbenz[e]indolone analogue of duocarmycin AS-I-145
    Konstantinos Kiakos
    Cancer Research Drug DNA Interactions Research Group, Department of Oncology, University College London, London, United Kingdom
    Mol Cancer Ther 6:2708-18. 2007
    ..adduct elimination occurred in a transcription-coupled manner and was dependent on a functional NER pathway and Rad18. The involvement of NER as the predominant excision pathway was confirmed in mammalian DNA repair mutant cells...
  69. ncbi UV sensitive mutations in histone H3 in Saccharomyces cerevisiae that alter specific K79 methylation states genetically act through distinct DNA repair pathways
    Margery L Evans
    Department of Biology, Denison University, Granville, OH 43023, USA
    Curr Genet 53:259-74. 2008
    ....
  70. ncbi Identification of pathways controlling DNA damage induced mutation in Saccharomyces cerevisiae
    Ewa T Lis
    Department of Chemistry, The Scripps Research Institute, CB262R, 10550N Torrey Pines Road, La Jolla, CA 92037, United States
    DNA Repair (Amst) 7:801-10. 2008
    ....
  71. ncbi Analysis of the spontaneous mutator phenotype associated with 20S proteasome deficiency in S. cerevisiae
    Justyna McIntyre
    Institute of Biochemistry and Biophysics, Polish Academy of Sciences, 02 106 Warsaw, Poland
    Mutat Res 593:153-63. 2006
    ..occurring spontaneously in yeast cells deficient in 20S proteasome function are connected with the unique Rad6/Rad18-dependent error-prone translesion DNA synthesis (TLS) requiring the activities of both TLS polymerases: Pol eta ..
  72. ncbi Multiple pathways cooperate to facilitate DNA replication fork progression through alkylated DNA
    María Victoria Vázquez
    Centro de Biologia Molecular Severo Ochoa CSIC UAM, Cantoblanco, Madrid, Spain
    DNA Repair (Amst) 7:1693-704. 2008
    ....
  73. ncbi RAD6-RAD18-RAD5-pathway-dependent tolerance to chronic low-dose ultraviolet light
    Takashi Hishida
    Research Institute for Microbial Diseases, Osaka University, 3 1 Yamadaoka, Suita, Osaka 565 0871, Japan
    Nature 457:612-5. 2009
    ..Here we examine the response of yeast cells to CLUV and identify a key role for the RAD6-RAD18-RAD5 error-free postreplication repair (RAD6 error-free PRR) pathway in promoting cell growth and survival...
  74. ncbi Ubc9- and mms21-mediated sumoylation counteracts recombinogenic events at damaged replication forks
    Dana Branzei
    FIRC Institute of Molecular Oncology Foundation and Department of Biomedical Sciences and Biotechnology, Universita degli Studi di Milano, Via Adamello 16, 20139 Milan, Italy
    Cell 127:509-22. 2006
    ..Our results indicate that Ubc9- and Mms21-mediated sumoylation functions as a regulatory mechanism, different from that of replication checkpoints, to prevent pathological accumulation of cruciform structures at damaged forks...
  75. ncbi Isolation of the RAD18 gene of Saccharomyces cerevisiae and construction of rad18 deletion mutants
    F Fabre
    Institut Curie Biologie, Centre Universitaire, Orsay, France
    Mol Gen Genet 215:425-30. 1989
    The RAD18 gene of Saccharomyces cerevisiae is involved in mutagenic DNA repair. We describe its isolation from a yeast library introduced into the centromeric YCp50 vector, a low copy number plasmid...
  76. ncbi Suppression of genetic defects within the RAD6 pathway by srs2 is specific for error-free post-replication repair but not for damage-induced mutagenesis
    Stacey Broomfield
    Department of Microbiology and Immunology, University of Saskatchewan, 107 Wiggins Road, Saskatoon, SK S7N 5E5, Canada
    Nucleic Acids Res 30:732-9. 2002
    srs2 was isolated during a screen for mutants that could suppress the UV-sensitive phenotype of rad6 and rad18 cells...
  77. ncbi A biological network in Saccharomyces cerevisiae prevents the deleterious effects of endogenous oxidative DNA damage
    Meng Er Huang
    Ludwig Institute for Cancer Research, CMME 3058, 9500 Gilman Drive, La Jolla, California 92093, USA
    Mol Cell 17:709-20. 2005
    ..These findings may provide insight in understanding the consequences of various pathophysiological processes in regard to genomic instability...
  78. ncbi Cooperation of replication protein A with the ubiquitin ligase Rad18 in DNA damage bypass
    Diana Huttner
    Cancer Research UK, London Research Institute, Clare Hall Laboratories, South Mimms, Herts, UK
    Cell Cycle 7:3629-33. 2008
    ..Both in yeast and in mammalian cells, RPA physically interacts with Rad18, the ubiquitin ligase responsible for PCNA mono-ubiquitylation...
  79. ncbi The RAD24 (= Rs1) gene product of Saccharomyces cerevisiae participates in two different pathways of DNA repair
    F Eckardt-Schupp
    Genetics 115:83-90. 1987
    ..Properties of the mutant are discussed which hint at the control of late steps in the pathways...

Research Grants6

  1. REPAIR PATHWAYS FOR IONIZING RADIATION DAMAGE IN YEAST
    John Game; Fiscal Year: 2002
    ..In a related aim, the order of gene function for RAD5O and RAD54 will be tested using different switching regimes with double mutants containing conditional alleles with differing permissive conditions. ..
  2. Repair Pathways for Ionizing Radiation Damage Yeast
    John Game; Fiscal Year: 2006
    ..Recent and existing mutants will be studied in detail with this system to determine the molecular involvement of each gene in DSB repair, sister chromatid exchange and recombination between chromosomes. ..