Home LiteratureArticle Details
PMID: 11953321 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Saccharomyces cerevisiae MGS1 is essential in strains deficient in the RAD6-dependent DNA damage tolerance pathway.

The EMBO journal ·Vol. 21 ·No. 8 ·2002-04-15 ·Pages 2019-29

Hishida T, Ohno T, Iwasaki H, Shinagawa H

Abstract

Saccharomyces cerevisiae Mgs1 protein, which possesses DNA-dependent ATPase and single strand DNA annealing activities, plays a role in maintaining genomic stability. 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 replication. The mgs1 mutant is not sensitive to DNA-damaging agents, but the mgs1 rad5 double mutant has increased sensitivity to hydroxyurea and a greatly increased spontaneous mutation rate. Growth defects of mgs1 rad18 double mutants are suppressed by a mutation in SRS2, encoding a DNA helicase, or by overexpression of Rad52. More over, mgs1 mutation suppresses the temperature sensitivity of mutants in POL3, encoding DNA polymerase delta. mgs1 also suppresses the growth defect of a pol3 mutant caused by expression of Escherichia coli RuvC, a bacterial Holliday junction resolvase. These findings suggest that Mgs1 is essential for preventing genome instability caused by replication fork arrest in cells deficient in the RAD6 pathway and may modulate replication fork movement catalyzed by yeast polymerase delta.

MeSH Terms
Adenosine Triphosphatases/genetics,metabolism Bacterial Proteins/genetics,metabolism Cell Cycle DNA Damage DNA Helicases/genetics,metabolism DNA Polymerase III/genetics,metabolism DNA-Binding Proteins/genetics,metabolism Endodeoxyribonucleases/genetics,metabolism Epistasis, Genetic Escherichia coli/enzymology,genetics Escherichia coli Proteins Fungal Proteins/genetics,metabolism Ligases/genetics,metabolism Mutagenesis Rad52 DNA Repair and Recombination Protein Recombination, Genetic Saccharomyces cerevisiae/enzymology,genetics,growth & development Saccharomyces cerevisiae Proteins Signal Transduction Temperature Ubiquitin/metabolism Ubiquitin-Conjugating Enzymes
Chemicals
Bacterial Proteins DNA-Binding Proteins Escherichia coli Proteins Fungal Proteins POL3 protein, S cerevisiae RAD18 protein, S cerevisiae RAD52 protein, S cerevisiae Rad52 DNA Repair and Recombination Protein Saccharomyces cerevisiae Proteins Ubiquitin ruvC protein, E coli RAD6 protein, S cerevisiae Ubiquitin-Conjugating Enzymes DNA Polymerase III Endodeoxyribonucleases Adenosine Triphosphatases MGS1 protein, S cerevisiae RAD5 protein, S cerevisiae DNA Helicases Ligases
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Hishida Takashi
Department of Molecular Microbiology, Research Institute for Microbial Diseases, Osaka University, Yamadaoka 3-1, Suita, Osaka 565-0871, Japan.
Ohno Takayuki
Iwasaki Hiroshi
Shinagawa Hideo
References (52)
52 references, click to expand
  1. The Werner syndrome protein is a DNA helicase.
    Nat Genet. 1997 Sep;17(1):100-3 PMID: 9288107
  2. Functional interaction between the Werner Syndrome protein and DNA polymerase delta.
    Proc Natl Acad Sci U S A. 2000 Apr 25;97(9):4603-8 PMID: 10781066
  3. SWI2/SNF2 and related proteins: ATP-driven motors that disrupt protein-DNA interactions?
    Cell. 1997 Mar 21;88(6):737-40 PMID: 9118215
  4. Yeast DNA repair proteins Rad6 and Rad18 form a heterodimer that has ubiquitin conjugating, DNA binding, and ATP hydrolytic activities.
    J Biol Chem. 1997 Sep 12;272(37):23360-5 PMID: 9287349
  5. Mutations in the RNA polymerase II transcription machinery suppress the hyperrecombination mutant hpr1 delta of Saccharomyces cerevisiae.
    Genetics. 1996 Mar;142(3):749-59 PMID: 8849885
  6. Nucleotide sequence and characterization of temperature-sensitive pol1 mutants of Saccharomyces cerevisiae.
    Gene. 1990 May 31;90(1):99-104 PMID: 2199334
  7. Genetic interactions between mutants of the 'error-prone' repair group of Saccharomyces cerevisiae and their effect on recombination and mutagenesis.
    Mutat Res. 1998 Mar;407(2):135-45 PMID: 9637242
  8. 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.
    Genetics. 1997 Dec;147(4):1557-68 PMID: 9409821
  9. The importance of repairing stalled replication forks.
    Nature. 2000 Mar 2;404(6773):37-41 PMID: 10716434
  10. The distribution of the numbers of mutants in bacterial populations.
    J Genet. 1949 Dec;49(3):264-85 PMID: 24536673
  11. The Werner syndrome gene product co-purifies with the DNA replication complex and interacts with PCNA and topoisomerase I.
    J Biol Chem. 1999 Dec 31;274(53):37795-9 PMID: 10608841
  12. The Werner syndrome gene: the molecular basis of RecQ helicase-deficiency diseases.
    Trends Genet. 2000 May;16(5):213-20 PMID: 10782115
  13. Mus81-Eme1 are essential components of a Holliday junction resolvase.
    Cell. 2001 Nov 16;107(4):537-48 PMID: 11719193
  14. The RFC2 gene, encoding the third-largest subunit of the replication factor C complex, is required for an S-phase checkpoint in Saccharomyces cerevisiae.
    Mol Cell Biol. 1998 Aug;18(8):4914-23 PMID: 9671499
  15. The Saccharomyces cerevisiae RAD6 group is composed of an error-prone and two error-free postreplication repair pathways.
    Genetics. 2000 Aug;155(4):1633-41 PMID: 10924462
  16. Metabolic suppressors of trimethoprim and ultraviolet light sensitivities of Saccharomyces cerevisiae rad6 mutants.
    J Bacteriol. 1979 Sep;139(3):866-76 PMID: 383698
  17. Rad51 protein involved in repair and recombination in S. cerevisiae is a RecA-like protein.
    Cell. 1992 May 1;69(3):457-70 PMID: 1581961
  18. A system of shuttle vectors and yeast host strains designed for efficient manipulation of DNA in Saccharomyces cerevisiae.
    Genetics. 1989 May;122(1):19-27 PMID: 2659436
  19. DNA recombination: the replication connection.
    Trends Biochem Sci. 1999 Jul;24(7):271-5 PMID: 10390616
  20. DNA repair genes and proteins of Saccharomyces cerevisiae.
    Annu Rev Genet. 1993;27:33-70 PMID: 8122907
  21. Circles: the replication-recombination-chromosome segregation connection.
    Proc Natl Acad Sci U S A. 2001 Jul 17;98(15):8189-95 PMID: 11459952
  22. Purification and characterization of the SRS2 DNA helicase of the yeast Saccharomyces cerevisiae.
    J Biol Chem. 1993 Jan 15;268(2):1252-9 PMID: 8419328
  23. Elevated recombination rates in transcriptionally active DNA.
    Cell. 1989 Feb 24;56(4):619-30 PMID: 2645056
  24. Holliday junctions accumulate in replication mutants via a RecA homolog-independent mechanism.
    Cell. 1997 Jul 11;90(1):87-96 PMID: 9230305
  25. A yeast gene, MGS1, encoding a DNA-dependent AAA(+) ATPase is required to maintain genome stability.
    Proc Natl Acad Sci U S A. 2001 Jul 17;98(15):8283-9 PMID: 11459965
  26. Two RING finger proteins mediate cooperation between ubiquitin-conjugating enzymes in DNA repair.
    EMBO J. 2000 Jul 3;19(13):3388-97 PMID: 10880451
  27. Partial suppression of the fission yeast rqh1(-) phenotype by expression of a bacterial Holliday junction resolvase.
    EMBO J. 2000 Jun 1;19(11):2751-62 PMID: 10835372
  28. Regulatable promoters of Saccharomyces cerevisiae: comparison of transcriptional activity and their use for heterologous expression.
    Nucleic Acids Res. 1994 Dec 25;22(25):5767-8 PMID: 7838736
  29. Positional cloning of the Werner's syndrome gene.
    Science. 1996 Apr 12;272(5259):258-62 PMID: 8602509
  30. Yeast DNA repair protein RAD5 that promotes instability of simple repetitive sequences is a DNA-dependent ATPase.
    J Biol Chem. 1994 Nov 11;269(45):28259-62 PMID: 7961763
  31. Involvement of the yeast DNA polymerase delta in DNA repair in vivo.
    Genetics. 1997 Aug;146(4):1239-51 PMID: 9258670
  32. A rapid method for localized mutagenesis of yeast genes.
    Yeast. 1992 Feb;8(2):79-82 PMID: 1561838
  33. Characterization of postreplication repair in Saccharomyces cerevisiae and effects of rad6, rad18, rev3 and rad52 mutations.
    Mol Gen Genet. 1981;184(3):471-8 PMID: 7038396
  34. MMS2, encoding a ubiquitin-conjugating-enzyme-like protein, is a member of the yeast error-free postreplication repair pathway.
    Proc Natl Acad Sci U S A. 1998 May 12;95(10):5678-83 PMID: 9576943
  35. Immunolocalization of Kex2 protease identifies a putative late Golgi compartment in the yeast Saccharomyces cerevisiae.
    J Cell Biol. 1991 May;113(3):527-38 PMID: 2016334
  36. Specific complex formation between yeast RAD6 and RAD18 proteins: a potential mechanism for targeting RAD6 ubiquitin-conjugating activity to DNA damage sites.
    Genes Dev. 1994 Apr 1;8(7):811-20 PMID: 7926769
  37. CDC45, a novel yeast gene that functions with the origin recognition complex and Mcm proteins in initiation of DNA replication.
    Mol Cell Biol. 1997 Feb;17(2):553-63 PMID: 9001208
  38. Genetic analysis of yeast RPA1 reveals its multiple functions in DNA metabolism.
    Genetics. 1998 Mar;148(3):989-1005 PMID: 9539419
  39. 5-Fluoroorotic acid as a selective agent in yeast molecular genetics.
    Methods Enzymol. 1987;154:164-75 PMID: 3323810
  40. Primary structure of the RAD52 gene in Saccharomyces cerevisiae.
    Mol Cell Biol. 1984 Dec;4(12):2735-44 PMID: 6098821
  41. A plethora of lesion-replicating DNA polymerases.
    Genes Dev. 1999 Sep 1;13(17):2191-5 PMID: 10485842
  42. RADH, a gene of Saccharomyces cerevisiae encoding a putative DNA helicase involved in DNA repair. Characteristics of radH mutants and sequence of the gene.
    Nucleic Acids Res. 1989 Sep 25;17(18):7211-9 PMID: 2552405
  43. UBC13, a DNA-damage-inducible gene, is a member of the error-free postreplication repair pathway in Saccharomyces cerevisiae.
    Curr Genet. 2000 Mar;37(3):168-74 PMID: 10794173
  44. Genetic mapping of the Saccharomyces cerevisiae DNA polymerase I gene and characterization of a pol1 temperature-sensitive mutant altered in DNA primase-polymerase complex stability.
    Mol Gen Genet. 1988 Jun;212(3):459-65 PMID: 3047550
  45. The YDp plasmids: a uniform set of vectors bearing versatile gene disruption cassettes for Saccharomyces cerevisiae.
    Yeast. 1991 Jul;7(5):475-7 PMID: 1897313
  46. MUS81 encodes a novel helix-hairpin-helix protein involved in the response to UV- and methylation-induced DNA damage in Saccharomyces cerevisiae.
    Mol Gen Genet. 2000 Jun;263(5):812-27 PMID: 10905349
  47. DNA damage-induced mutation: tolerance via translesion synthesis.
    Mutat Res. 2000 Jun 30;451(1-2):169-85 PMID: 10915871
  48. The srs2 suppressor of UV sensitivity acts specifically on the RAD5- and MMS2-dependent branch of the RAD6 pathway.
    Nucleic Acids Res. 2001 Sep 1;29(17):3487-94 PMID: 11522817
  49. DNA replication meets genetic exchange: chromosomal damage and its repair by homologous recombination.
    Proc Natl Acad Sci U S A. 2001 Jul 17;98(15):8461-8 PMID: 11459990
  50. The SRS2 suppressor of rad6 mutations of Saccharomyces cerevisiae acts by channeling DNA lesions into the RAD52 DNA repair pathway.
    Genetics. 1990 Apr;124(4):817-31 PMID: 2182387
  51. Initiation of genetic recombination and recombination-dependent replication.
    Trends Biochem Sci. 2000 Apr;25(4):156-65 PMID: 10754547
  52. A novel protein interacts with the Werner's syndrome gene product physically and functionally.
    J Biol Chem. 2001 Jun 8;276(23):20364-9 PMID: 11301316
Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/21.8.2019
Published
2002-04-15
Pages
2019-29
Language
English
Region
England
NLM ID
8208664
PMCID
PMC125966
Subset
IM
External Links
PubMed source DOI: 10.1093/emboj/21.8.2019 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2