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Proc Natl Acad Sci U S A. 2004 Sep 28;101(39):14174-9. Epub 2004 Sep 16.

MutS inhibits RecA-mediated strand exchange with platinated DNA substrates.

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  • 1Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA.

Abstract

Human cell lines and Escherichia coli dam mutants are sensitive to the cytotoxic action of the anticancer agent, cisplatin. Introduction of mutations disabling DNA mismatch repair into these cell lines renders them resistant to the action of this drug. We used RecA-mediated strand exchange between homologous phiX174 molecules, one that was platinated and the other that was unmodified, to show that strand transfer is decreased in a dose-dependent manner. Transfer was severely decreased at 10 adducts per molecule (5,386 bp) and abolished with 24 adducts. At low levels of adduction, addition of MutS to the reaction further decreases the rate and yield in a dose-dependent manner. MutL addition was without effect even in the presence of MutS. The results suggest that although mismatch repair is beneficial for mutation avoidance, its antirecombination activity on inappropriate substrates can be lethal to the cell.

PMID:
15375217
PMCID:
PMC521133
DOI:
10.1073/pnas.0406104101
[PubMed - indexed for MEDLINE]
Free PMC Article
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