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PMID: 16193328 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Roles of SGS1, MUS81, and RAD51 in the repair of lagging-strand replication defects in Saccharomyces cerevisiae.

Current genetics ·Vol. 48 ·No. 4 ·2005-10-00 ·Pages 213-25

Ii M, Brill SJ

Abstract

Yeast cells lacking the SGS1 DNA helicase and the MUS81 structure-specific endonuclease display a synthetic lethality that is suppressed by loss of the RAD51 recombinase. This epistatic interaction suggests that the primary function of SGS1 or MUS81, or both genes, is downstream of RAD51. To identify RAD51-independent functions of SGS1 and MUS81, a synthetic-lethal screen was performed on the sgs1 mus81 rad51triple mutant. We found that mutation of RNH202, which encodes a subunit of the hetero-trimeric RNase H2, generates a profound synthetic-sickness in this background. RNase H2 is thought to play a non-essential role in Okazaki fragment maturation. Cells lacking RNH202 showed synthetic growth defects when combined with either mus81 or sgs1 alone. But, whereas the loss of RAD51 had little effect on rnh202 sgs1 double mutants, it strongly inhibited the growth of rnh202 mus81 cells. These data indicate that the primary function of SGS1, but not MUS81, is downstream of RAD51. SGS1 must have some RAD51-independent function, however, since the growth of rnh202 mus81 rad51cells was further compromised by the loss of SGS1. Consistent with these results, we show that rnh202 cells display a sensitivity to DNA-damaging agents that is exacerbated in the absence of RAD51 or MUS81. These data support a model in which defects in lagging-strand replication are repaired by the Mus81 endonuclease or through a pathway dependent on Rad51 and Sgs1.

MeSH Terms
DNA Helicases/genetics DNA Repair/genetics DNA Replication/genetics DNA-Binding Proteins/genetics Endonucleases/genetics Genomic Instability/genetics Models, Genetic Mutagens/pharmacology Mutant Proteins/metabolism Rad51 Recombinase/genetics RecQ Helicases Ribonuclease H/genetics,metabolism Saccharomyces cerevisiae/genetics Saccharomyces cerevisiae Proteins/genetics Telomere/physiology
Chemicals
DNA-Binding Proteins Mutagens Mutant Proteins Saccharomyces cerevisiae Proteins RAD51 protein, S cerevisiae Rad51 Recombinase Endonucleases MUS81 protein, S cerevisiae ribonuclease HII Ribonuclease H SGS1 protein, S cerevisiae DNA Helicases RecQ Helicases
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Ii Miki
Department of Molecular Biology and Biochemistry, Rutgers University, 679 Hoes Lane, Piscataway, NJ 08854, USA.
Brill Steven J
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Article Info
Journal
Current genetics
Abbr.
Curr Genet
ISSN
0172-8083
DOI
10.1007/s00294-005-0014-5
Published
2005-10-00
Epub
2005-00-04
Pages
213-25
Language
English
Region
United States
NLM ID
8004904
PMCID
PMC1828632
Subset
IM
Grants
NIGMS NIH HHS · R01 GM067956 · United States
NIGMS NIH HHS · GM067956 · United States
External Links
PubMed source DOI: 10.1007/s00294-005-0014-5 PMC Full Text View journal details
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