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PMID: 15199178 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Heteroduplex rejection during single-strand annealing requires Sgs1 helicase and mismatch repair proteins Msh2 and Msh6 but not Pms1.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 101 ·No. 25 ·2004-06-22 ·Pages 9315-20

Sugawara N, Goldfarb T, Studamire B, Alani E, Haber JE

Abstract

Recombination between moderately divergent DNA sequences is impaired compared with identical sequences. In yeast, an HO endonuclease-induced double-strand break can be repaired by single-strand annealing (SSA) between flanking homologous sequences. A 3% sequence divergence between 205-bp sequences flanking the double-strand break caused a 6-fold reduction in repair compared with identical sequences. This reduction in heteroduplex rejection was suppressed in a mismatch repair-defective msh6 Delta strain and partially suppressed in an msh2 separation-of-function mutant. In mlh1 Delta strains, heteroduplex rejection was greater than in msh6 Delta strains but less than in wild type. Deleting PMS1, MLH2,or MLH3 had no effect on heteroduplex rejection, but a pms1 Delta mlh2 Delta mlh3 Delta triple mutant resembled mlh1 Delta. However, correction of the mismatches within heteroduplex SSA intermediates required PMS1 and MLH1 to the same extent as MSH2 and MSH6. An SSA competition assay in which either diverged or identical repeats can be used for repair showed that heteroduplex DNA is likely to be unwound rather than degraded. This conclusion is supported by the finding that deleting the SGS1 helicase also suppressed heteroduplex rejection.

MeSH Terms
Base Pair Mismatch/genetics Carrier Proteins/genetics,metabolism DNA Helicases/metabolism DNA Primers DNA Repair/genetics DNA-Binding Proteins/genetics,metabolism Fungal Proteins/genetics,metabolism Genotype MutL Proteins MutS Homolog 2 Protein Mutagenesis Nucleic Acid Heteroduplexes/genetics RecQ Helicases Saccharomyces cerevisiae/genetics Saccharomyces cerevisiae Proteins/genetics,metabolism Sequence Deletion
Chemicals
Carrier Proteins DNA Primers DNA-Binding Proteins Fungal Proteins MSH6 protein, S cerevisiae Nucleic Acid Heteroduplexes PMS1 protein, S cerevisiae Saccharomyces cerevisiae Proteins SGS1 protein, S cerevisiae MSH2 protein, S cerevisiae MutL Proteins MutS Homolog 2 Protein DNA Helicases RecQ Helicases
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Sugawara Neal
Rosenstiel Center and Department of Biology, Brandeis University, Waltham, MA 02454-9110, USA.
Goldfarb Tamara
Studamire Barbara
Alani Eric
Haber James E
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0305749101
Published
2004-06-22
Epub
2004-00-15
Pages
9315-20
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC438974
Subset
IM
Grants
NIGMS NIH HHS · GM20056 · United States
NIGMS NIH HHS · R01 GM053085 · United States
NIGMS NIH HHS · GM53085 · United States
NIGMS NIH HHS · R37 GM020056 · United States
NIGMS NIH HHS · R01 GM020056 · United States
External Links
PubMed source DOI: 10.1073/pnas.0305749101 PMC Full Text View journal details
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