methyl methanesulfonate


Summary: An alkylating agent in cancer therapy that may also act as a mutagen by interfering with and causing damage to DNA.

Top Publications

  1. Shi Q, Wang Y, Zheng X, Lee R, Wang Y. Critical role of DNA checkpoints in mediating genotoxic-stress-induced filamentous growth in Candida albicans. Mol Biol Cell. 2007;18:815-26 pubmed
    ..albicans. ..
  2. Bermúdez López M, Ceschia A, De Piccoli G, Colomina N, Pasero P, Aragon L, et al. The Smc5/6 complex is required for dissolution of DNA-mediated sister chromatid linkages. Nucleic Acids Res. 2010;38:6502-12 pubmed publisher
    ..We propose that Smc5/6 has an essential role in the removal of DNA-mediated linkages to prevent chromosome missegregation and aneuploidy. ..
  3. Resende F, Tomazella I, Barbosa L, Ponce M, Furtado R, Pereira A, et al. Effect of the dibenzylbutyrolactone lignan (-)-hinokinin on doxorubicin and methyl methanesulfonate clastogenicity in V79 Chinese hamster lung fibroblasts. Mutat Res. 2010;700:62-6 pubmed publisher
    ..genotoxicity and evaluated the compound's effect on the activity of the clastogens doxorubicin (DXR) and methyl methanesulfonate (MMS) in the micronucleus (MN) assay with Chinese hamster lung fibroblast V79 cells...
  4. Gassman N, Stefanick D, Kedar P, Horton J, Wilson S. Hyperactivation of PARP triggers nonhomologous end-joining in repair-deficient mouse fibroblasts. PLoS ONE. 2012;7:e49301 pubmed publisher
    ..extent and duration of PARP-1 activation was measured after exposure to either the DNA alkylating agent, methyl methanesulfonate (MMS), or to low energy laser-induced DNA damage...
  5. Wyatt M, Pittman D. Methylating agents and DNA repair responses: Methylated bases and sources of strand breaks. Chem Res Toxicol. 2006;19:1580-94 pubmed
  6. Ma W, Resnick M, Gordenin D. Apn1 and Apn2 endonucleases prevent accumulation of repair-associated DNA breaks in budding yeast as revealed by direct chromosomal analysis. Nucleic Acids Res. 2008;36:1836-46 pubmed publisher
    ..To investigate BER in vivo, we examined the repair of methyl methanesulfonate (MMS) induced DNA damage in haploid G1 yeast cells, so that replication bypass and recombinational DSB ..
  7. Brown S, Niimi A, Lehmann A. Ubiquitination and deubiquitination of PCNA in response to stalling of the replication fork. Cell Cycle. 2009;8:689-92 pubmed
    ..have shown that this modification of PCNA is necessary for the survival of cells after UV-irradiation and methyl methanesulfonate, that it is independent of cell cycle checkpoint activation, and that it persists after UV damage has ..
  8. Jung H, Lee J, Seo Y. Enhancement of methyl methanesulfonate-induced base excision repair in the presence of selenomethionine on p53-dependent pathway. J Med Food. 2009;12:340-4 pubmed publisher
    ..When methyl methanesulfonate, a BER-inducing agent, was treated in the cells, DNA damage was rapidly decreased in the presence of ..
  9. Workman C, Mak H, McCuine S, Tagne J, Agarwal M, Ozier O, et al. A systems approach to mapping DNA damage response pathways. Science. 2006;312:1054-9 pubmed
    ..Validated interactions were assembled into causal pathway models that provide global hypotheses of how signaling, transcription, and phenotype are integrated after damage. ..

More Information


  1. Chang Y, Gong L, Yuan W, Li X, Chen G, Li X, et al. Replication protein A (RPA1a) is required for meiotic and somatic DNA repair but is dispensable for DNA replication and homologous recombination in rice. Plant Physiol. 2009;151:2162-73 pubmed publisher
    ..mutant was hypersensitive to ultraviolet-C irradiation and the DNA-damaging agents mitomycin C and methyl methanesulfonate. Thus, our data suggest that OsRPA1a plays an essential role in DNA repair but may not participate in, or ..
  2. Budd M, Reis C, Smith S, Myung K, Campbell J. Evidence suggesting that Pif1 helicase functions in DNA replication with the Dna2 helicase/nuclease and DNA polymerase delta. Mol Cell Biol. 2006;26:2490-500 pubmed
  3. Hanssen Bauer A, Solvang Garten K, Gilljam K, Torseth K, Wilson D, Akbari M, et al. The region of XRCC1 which harbours the three most common nonsynonymous polymorphic variants, is essential for the scaffolding function of XRCC1. DNA Repair (Amst). 2012;11:357-66 pubmed publisher
    ..Also, we found that ectopic expression of the region from residue 166-436 partially rescued the methyl methanesulfonate (MMS) hypersensitivity of XRCC1-deficient EM9 cells, suggesting a key role for this region in mediating ..
  4. Hu T, Kaluzhny Y, Mun G, Barnett B, Karetsky V, Wilt N, et al. Intralaboratory and interlaboratory evaluation of the EpiDerm 3D human reconstructed skin micronucleus (RSMN) assay. Mutat Res. 2009;673:100-8 pubmed publisher
    ..Three model genotoxins, mitomycin C (MMC), vinblastine sulfate (VB) and methyl methanesulfonate (MMS) induced significant, dose-related increases in cytotoxicity and MN induction in EpiDerm tissues...
  5. Hosseinzadeh H, Sadeghnia H. Effect of safranal, a constituent of Crocus sativus (saffron), on methyl methanesulfonate (MMS)-induced DNA damage in mouse organs: an alkaline single-cell gel electrophoresis (comet) assay. DNA Cell Biol. 2007;26:841-6 pubmed
    The influence of safranal, a constituent of Crocus sativus L. stigmas, on methyl methanesulfonate (MMS)-induced DNA damage was examined using alkaline single-cell gel electrophoresis (SCGE), or comet, assay in multiple organs of mice (..
  6. Mankouri H, Ngo H, Hickson I. Shu proteins promote the formation of homologous recombination intermediates that are processed by Sgs1-Rmi1-Top3. Mol Biol Cell. 2007;18:4062-73 pubmed
    ..We propose a model in which the Shu proteins act in HRR to promote the formation of HRR intermediates that are processed by the Sgs1-Rmi1-Top3 complex. ..
  7. Jiang Y, Zhang X, Sun L, Zhang G, DUERKSEN HUGHES P, Zhu X, et al. Methyl methanesulfonate induces apoptosis in p53-deficient H1299 and Hep3B cells through a caspase 2- and mitochondria-associated pathway. Environ Toxicol Pharmacol. 2012;34:694-704 pubmed publisher
    b>Methyl methanesulfonate (MMS) has been shown to induce apoptosis in various cell types through p53-dependent pathways...
  8. O Neill B, Szyjka S, Lis E, Bailey A, Yates J, Aparicio O, et al. Pph3-Psy2 is a phosphatase complex required for Rad53 dephosphorylation and replication fork restart during recovery from DNA damage. Proc Natl Acad Sci U S A. 2007;104:9290-5 pubmed
    ..These findings suggest that Rad53 regulates replication fork restart and initiation of late firing origins independently and that regulation of these processes is mediated by specific Rad53 phosphatases. ..
  9. Yang Y, Gordenin D, Resnick M. A single-strand specific lesion drives MMS-induced hyper-mutability at a double-strand break in yeast. DNA Repair (Amst). 2010;9:914-21 pubmed publisher
    ..Here, we establish that the generation of LHM by methyl methanesulfonate (MMS) during repair of a chromosomal double-strand break (DSB) can result in over 0...
  10. Kanamitsu K, Ikeda S. Fission yeast homologs of human XPC and CSB, rhp41 and rhp26, are involved in transcription-coupled repair of methyl methanesulfonate-induced DNA damage. Genes Genet Syst. 2011;86:83-91 pubmed
    b>Methyl methanesulfonate (MMS) methylates nitrogen atoms in purines, and predominantly produces 7-methylguanine and 3-methyladenine (3-meA)...
  11. Ma W, Panduri V, Sterling J, Van Houten B, Gordenin D, Resnick M. The transition of closely opposed lesions to double-strand breaks during long-patch base excision repair is prevented by the coordinated action of DNA polymerase delta and Rad27/Fen1. Mol Cell Biol. 2009;29:1212-21 pubmed publisher
    ..This contrasts with the efficient repair of nonclustered methyl methanesulfonate-induced lesions, as measured by quantitative PCR and S1 nuclease cleavage of single-strand break sites...
  12. Yang H, Yang T, Baur J, Perez E, Matsui T, Carmona J, et al. Nutrient-sensitive mitochondrial NAD+ levels dictate cell survival. Cell. 2007;130:1095-107 pubmed
    ..We discuss the relevance of these findings to understanding how nutrition modulates physiology and to the evolution of apoptosis. ..
  13. McNeill D, Wilson D. A dominant-negative form of the major human abasic endonuclease enhances cellular sensitivity to laboratory and clinical DNA-damaging agents. Mol Cancer Res. 2007;5:61-70 pubmed
    ..ED in Chinese hamster ovary cells enhances the cytotoxic effects of the laboratory DNA-damaging agents, methyl methanesulfonate (MMS; 5.4-fold) and hydrogen peroxide (1.5-fold)...
  14. Holway A, Kim S, La Volpe A, Michael W. Checkpoint silencing during the DNA damage response in Caenorhabditis elegans embryos. J Cell Biol. 2006;172:999-1008 pubmed
    ..They also show that checkpoint activation is not an obligatory response to DNA damage and that pathways exist to bypass the checkpoint when survival depends on uninterrupted progression through the cell cycle. ..
  15. Branda R, O Neill J, Brooks E, Powden C, Naud S, Nicklas J. The effect of dietary folic acid deficiency on the cytotoxic and mutagenic responses to methyl methanesulfonate in wild-type and in 3-methyladenine DNA glycosylase-deficient Aag null mice. Mutat Res. 2007;615:12-7 pubmed
    ..They were then treated with methyl methanesulfonate (MMS), 100mg/kg i.p...
  16. Tomizawa Y, Ui A, Onoda F, Ogiwara H, Tada S, Enomoto T, et al. Rad50 is involved in MMS-induced recombination between homologous chromosomes in mitotic cells. Genes Genet Syst. 2007;82:157-60 pubmed
    ..of recombination between homologous chromosomes in cells in the vegetative growth state upon exposure to methyl methanesulfonate. However, UV-induced recombination between homologous chromosomes is intact in both rad50 and smc6-56 ..
  17. Kitanovic A, Walther T, Loret M, Holzwarth J, Kitanovic I, Bonowski F, et al. Metabolic response to MMS-mediated DNA damage in Saccharomyces cerevisiae is dependent on the glucose concentration in the medium. FEMS Yeast Res. 2009;9:535-51 pubmed publisher
    ..Our results clearly demonstrate that calorie restriction reduces MMS toxicity through increased respiration and reduced ROS accumulation, enhancing the survival and recovery of cells. ..
  18. Sagan D, Müller R, Kröger C, Hematulin A, Mörtl S, Eckardt Schupp F. The DNA repair protein NBS1 influences the base excision repair pathway. Carcinogenesis. 2009;30:408-15 pubmed publisher
    ..poly-(adenosine diphosphate-ribose)-polymerase-1 (PARP1) following genotoxic treatment with H(2)O(2) or methyl methanesulfonate, indicating impaired processing of damaged bases by BER as PARP1 activity is stimulated by the single-..
  19. Rowe L, Degtyareva N, Doetsch P. Yap1: a DNA damage responder in Saccharomyces cerevisiae. Mech Ageing Dev. 2012;133:147-56 pubmed publisher
    ..Our findings reveal an epistatic link between Yap1 and the DNA base excision repair pathway. Corruption of the Yap1-mediated DNA damage response influences cell survival and genomic stability in response to exposure to genotoxic agents. ..
  20. Harrigan J, Wilson D, Prasad R, Opresko P, Beck G, May A, et al. The Werner syndrome protein operates in base excision repair and cooperates with DNA polymerase beta. Nucleic Acids Res. 2006;34:745-54 pubmed
    ..RNA technology, we demonstrate that WRN knockdown cells are hypersensitive to the alkylating agent methyl methanesulfonate, which creates DNA damage that is primarily repaired by the BER pathway...
  21. Nikolova T, Ensminger M, Lobrich M, Kaina B. Homologous recombination protects mammalian cells from replication-associated DNA double-strand breaks arising in response to methyl methanesulfonate. DNA Repair (Amst). 2010;9:1050-63 pubmed publisher
    ..end-joining (NHEJ) or both are involved in the repair of DSBs formed following treatment of cells with methyl methanesulfonate (MMS)...
  22. Hastie C, Vázquez Martin C, Philp A, Stark M, Cohen P. The Saccharomyces cerevisiae orthologue of the human protein phosphatase 4 core regulatory subunit R2 confers resistance to the anticancer drug cisplatin. FEBS J. 2006;273:3322-34 pubmed
    ..By comparison with the yeast system, this complex may confer resistance to cisplatin in higher eukaryotes. ..
  23. Staszewski O, Nikolova T, Kaina B. Kinetics of gamma-H2AX focus formation upon treatment of cells with UV light and alkylating agents. Environ Mol Mutagen. 2008;49:734-40 pubmed publisher
    ..Here we show that DNA damage induced by alkylating agents [methyl methanesulfonate (MMS) and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)] and ultraviolet light (UV-C) leads to a dose and ..
  24. Brem R, Fernet M, Chapot B, Hall J. The methyl methanesulfonate induced S-phase delay in XRCC1-deficient cells requires ATM and ATR. DNA Repair (Amst). 2008;7:849-57 pubmed publisher
    ..genetic instability and a significant delay in S-phase progression after exposure to the alkylating agent methyl methanesulfonate (MMS)...
  25. Ramakrishna K, Raman N, Rao K, Prasad A, Reddy K. Development and validation of GC-MS method for the determination of methyl methanesulfonate and ethyl methanesulfonate in imatinib mesylate. J Pharm Biomed Anal. 2008;46:780-3 pubmed publisher
    ..b>methyl methanesulfonate (MMS) and ethyl methanesulfonate (EMS) in imatinib mesylate (INM)...
  26. Shen C, Lancaster C, Shi B, Guo H, Thimmaiah P, Bjornsti M. TOR signaling is a determinant of cell survival in response to DNA damage. Mol Cell Biol. 2007;27:7007-17 pubmed
    ..In the presence of the DNA-damaging agent methyl methanesulfonate (MMS), TOR-dependent cell survival required a functional S-phase checkpoint...
  27. Lundin C, North M, Erixon K, Walters K, Jenssen D, Goldman A, et al. Methyl methanesulfonate (MMS) produces heat-labile DNA damage but no detectable in vivo DNA double-strand breaks. Nucleic Acids Res. 2005;33:3799-811 pubmed
    Homologous recombination (HR) deficient cells are sensitive to methyl methanesulfonate (MMS)...
  28. St Onge R, Mani R, Oh J, Proctor M, Fung E, Davis R, et al. Systematic pathway analysis using high-resolution fitness profiling of combinatorial gene deletions. Nat Genet. 2007;39:199-206 pubmed
    ..interactions among 26 Saccharomyces cerevisiae genes conferring resistance to the DNA-damaging agent methyl methanesulfonate (MMS), as determined by chemogenomic fitness profiling of pooled deletion strains...
  29. Roberts T, Kobor M, Bastin Shanower S, Ii M, Horte S, Gin J, et al. Slx4 regulates DNA damage checkpoint-dependent phosphorylation of the BRCT domain protein Rtt107/Esc4. Mol Biol Cell. 2006;17:539-48 pubmed
  30. Rai G, Vyjayanti V, Dorjsuren D, Simeonov A, Jadhav A, Wilson D, et al. Synthesis, biological evaluation, and structure-activity relationships of a novel class of apurinic/apyrimidinic endonuclease 1 inhibitors. J Med Chem. 2012;55:3101-12 pubmed publisher
    ..Moreover, this class of compounds possesses a generally favorable in vitro ADME profile, along with good exposure levels in plasma and brain following intraperitoneal dosing (30 mg/kg body weight) in mice. ..
  31. Guruprasad K, Subramanian A, Singh V, Sharma R, Gopinath P, Sewram V, et al. Brahmarasayana protects against Ethyl methanesulfonate or Methyl methanesulfonate induced chromosomal aberrations in mouse bone marrow cells. BMC Complement Altern Med. 2012;12:113 pubmed
    ..The present study assessed the role of Brahmarasayana (BR) on Ethyl methanesulfonate (EMS)-and Methyl methanesulfonate (MMS)-induced genotoxicity and DNA repair in in vivo mouse test system...
  32. Luke B, Versini G, Jaquenoud M, Zaidi I, Kurz T, Pintard L, et al. The cullin Rtt101p promotes replication fork progression through damaged DNA and natural pause sites. Curr Biol. 2006;16:786-92 pubmed
    ..We therefore propose that the cullin Rtt101p promotes fork progression through obstacles such as DNA lesions or tightly bound protein-DNA complexes via a new mechanism involving ubiquitin-conjugation. ..
  33. Horton J, Stefanick D, Wilson S. Involvement of poly(ADP-ribose) polymerase activity in regulating Chk1-dependent apoptotic cell death. DNA Repair (Amst). 2005;4:1111-20 pubmed
    ..A highly cytotoxic concentration of the DNA methylating agent methyl methanesulfonate (MMS) results in cellular ATP depletion and cell death primarily by necrosis in both wild-type and DNA ..
  34. Smolka M, Albuquerque C, Chen S, Schmidt K, Wei X, Kolodner R, et al. Dynamic changes in protein-protein interaction and protein phosphorylation probed with amine-reactive isotope tag. Mol Cell Proteomics. 2005;4:1358-69 pubmed
  35. Laha S, Das S, Hajra S, Sau S, Sinha P. The budding yeast protein Chl1p is required to preserve genome integrity upon DNA damage in S-phase. Nucleic Acids Res. 2006;34:5880-91 pubmed
    ..Our work suggests that Chl1p is required for genome integrity when cells suffer endogenously or exogenously induced DNA damage. ..
  36. Doak S, Jenkins G, Johnson G, Quick E, Parry E, Parry J. Mechanistic influences for mutation induction curves after exposure to DNA-reactive carcinogens. Cancer Res. 2007;67:3904-11 pubmed
    ..A pragmatic threshold for carcinogenicity may therefore exist for such genotoxins. ..
  37. Lee M, Kim M, Kim H, Bae Y, Park J, Kwak J, et al. Alkylating agent methyl methanesulfonate (MMS) induces a wave of global protein hyperacetylation: implications in cancer cell death. Biochem Biophys Res Commun. 2007;360:483-9 pubmed
    ..In the present study, we found that an alkylating agent methyl methanesulfonate (MMS) induces a robust and reversible hyperacetylation of both cytoplasmic and nuclear proteins during ..
  38. Benton M, Somasundaram S, Glasner J, Palecek S. Analyzing the dose-dependence of the Saccharomyces cerevisiae global transcriptional response to methyl methanesulfonate and ionizing radiation. BMC Genomics. 2006;7:305 pubmed
    ..cerevisiae to multiple doses of two representative DNA damaging agents, methyl methanesulfonate (MMS) and gamma radiation...
  39. Horton J, Wilson S. Hypersensitivity phenotypes associated with genetic and synthetic inhibitor-induced base excision repair deficiency. DNA Repair (Amst). 2007;6:530-43 pubmed
    ..g., methyl methanesulfonate (MMS)...
  40. Morishita T, Furukawa F, Sakaguchi C, Toda T, Carr A, Iwasaki H, et al. Role of the Schizosaccharomyces pombe F-Box DNA helicase in processing recombination intermediates. Mol Cell Biol. 2005;25:8074-83 pubmed recombination repair, we isolated fission yeast Schizosaccharomyces pombe mutants sensitive to methyl methanesulfonate (MMS) and a synthetic lethal with rad2. A gene that complements such mutations was isolated from the S...
  41. Bandyopadhyay S, Mehta M, Kuo D, Sung M, Chuang R, Jaehnig E, et al. Rewiring of genetic networks in response to DNA damage. Science. 2010;330:1385-9 pubmed publisher
    ..Differential networks chart a new type of genetic landscape that is invaluable for mapping cellular responses to stimuli. ..
  42. Conde F, Ontoso D, Acosta I, Gallego Sánchez A, Bueno A, San Segundo P. Regulation of tolerance to DNA alkylating damage by Dot1 and Rad53 in Saccharomyces cerevisiae. DNA Repair (Amst). 2010;9:1038-49 pubmed publisher
    ..We propose that threshold levels of Rad53 activity exquisitely modulate the tolerance to alkylating damage at least by controlling the abundance of the key TLS factor Rev1 bound to chromatin. ..
  43. Kanamitsu K, Tanihigashi H, Tanita Y, Inatani S, Ikeda S. Involvement of 3-methyladenine DNA glycosylases Mag1p and Mag2p in base excision repair of methyl methanesulfonate-damaged DNA in the fission yeast Schizosaccharomyces pombe. Genes Genet Syst. 2007;82:489-94 pubmed
    ..The mag1 and mag2 single mutants as well as the double mutant showed no obvious methyl methanesulfonate (MMS) sensitivity...
  44. Cordon Preciado V, Ufano S, Bueno A. Limiting amounts of budding yeast Rad53 S-phase checkpoint activity results in increased resistance to DNA alkylation damage. Nucleic Acids Res. 2006;34:5852-62 pubmed
    ..In budding yeast, alkylating chemicals, such as methyl methanesulfonate (MMS), or depletion of nucleotides by hydroxyurea (HU) stall DNA replication forks and thus activate ..
  45. Nowosielska A, Smith S, Engelward B, Marinus M. Homologous recombination prevents methylation-induced toxicity in Escherichia coli. Nucleic Acids Res. 2006;34:2258-68 pubmed
  46. Komata M, Bando M, Araki H, Shirahige K. The direct binding of Mrc1, a checkpoint mediator, to Mcm6, a replication helicase, is essential for the replication checkpoint against methyl methanesulfonate-induced stress. Mol Cell Biol. 2009;29:5008-19 pubmed publisher
    ..showed a severe defect in DNA replication checkpoint activation in response to stress caused by methyl methanesulfonate. Interestingly, the mutant did not show any defect in DNA replication checkpoint activation in response ..
  47. Meira L, Moroski Erkul C, Green S, Calvo J, Bronson R, Shah D, et al. Aag-initiated base excision repair drives alkylation-induced retinal degeneration in mice. Proc Natl Acad Sci U S A. 2009;106:888-93 pubmed publisher
    ..Aag heterozygotes display an intermediate level of retinal degeneration, demonstrating haploinsufficiency and underscoring that Aag expression confers a dominant retinal degeneration phenotype. ..
  48. Gallego Sánchez A, Andrés S, Conde F, San Segundo P, Bueno A. Reversal of PCNA ubiquitylation by Ubp10 in Saccharomyces cerevisiae. PLoS Genet. 2012;8:e1002826 pubmed publisher
    ..Finally, we report that Ubp10 counteracts Rad18 E3-ubiquitin ligase activity on PCNA at lysine 164 in such a manner that deregulation of Ubp10 expression causes tolerance impairment and MMS hypersensitivity. ..
  49. Flott S, Alabert C, Toh G, Toth R, Sugawara N, Campbell D, et al. Phosphorylation of Slx4 by Mec1 and Tel1 regulates the single-strand annealing mode of DNA repair in budding yeast. Mol Cell Biol. 2007;27:6433-45 pubmed completing DNA synthesis during recovery from replisome stalling induced by the DNA alkylating agent methyl methanesulfonate (MMS)...
  50. Alabert C, Bianco J, Pasero P. Differential regulation of homologous recombination at DNA breaks and replication forks by the Mrc1 branch of the S-phase checkpoint. EMBO J. 2009;28:1131-41 pubmed publisher
    ..Taken together, these data indicate that the DNA replication checkpoint suppresses genomic instability in S phase by blocking recombination at chromosome breaks and permitting helpful recombination at stalled forks. ..
  51. Kim S, Michael W. Regulated proteolysis of DNA polymerase eta during the DNA-damage response in C. elegans. Mol Cell. 2008;32:757-66 pubmed publisher
    ..Implications for how this system may control the removal of POLH-1 from replication forks after TLS are discussed. ..
  52. Lupu A, Nevo E, Zamorzaeva I, Korol A. Ecological-genetic feedback in DNA repair in wild barley, Hordeum spontaneum. Genetica. 2006;127:121-32 pubmed
    ..Such a dependence of DNA integrity on environment and genotype may serve an important factor for maintaining relatively high level of mutability without increasing the genetic load. ..
  53. Barbour L, Ball L, Zhang K, Xiao W. DNA damage checkpoints are involved in postreplication repair. Genetics. 2006;174:1789-800 pubmed
    ..Epistatic analysis showed that rad9 is synergistic to both mms2 and rev3 with respect to killing by methyl methanesulfonate (MMS), and the triple mutant is nearly as sensitive as the rad18 single mutant...