Transfer of the MSH2.MSH6 complex from proliferating cell nuclear antigen to mispaired bases in DNA.
Proliferating cell nuclear antigen (PCNA) is thought to play a role in DNA mismatch repair at the DNA synthesis step as well as in an earlier step. Studies showing that PCNA interacts with mispair-binding protein complexes, MSH2.MSH3 and MSH2.MSH6, and that PCNA enhances MSH2.MSH6 mispair binding specificity suggest PCNA may ... be involved in mispair recognition. Here we show that PCNA and MSH2.MSH6 form a stable ternary complex with a homoduplex (G/C) DNA, but MSH2.MSH6 binding to a heteroduplex (G/T) DNA disrupts MSH2.MSH6 binding to PCNA. We also found that the addition of ATP or adenosine 5'-O-(thiotriphosphate) restores MSH2.MSH6 binding to PCNA, presumably by disrupting MSH2.MSH6 binding to the heteroduplex (G/T) DNA. These results support a model in which MSH2.MSH6 binds to PCNA loaded on newly replicated DNA and is transferred from PCNA to mispaired bases in DNA.
Mesh Terms:
Adenosine Triphosphate, Base Pair Mismatch, DNA, DNA Repair, DNA-Binding Proteins, Fungal Proteins, Macromolecular Substances, MutS Homolog 2 Protein, Nucleic Acid Heteroduplexes, Proliferating Cell Nuclear Antigen, Saccharomyces cerevisiae Proteins
Adenosine Triphosphate, Base Pair Mismatch, DNA, DNA Repair, DNA-Binding Proteins, Fungal Proteins, Macromolecular Substances, MutS Homolog 2 Protein, Nucleic Acid Heteroduplexes, Proliferating Cell Nuclear Antigen, Saccharomyces cerevisiae Proteins
J. Biol. Chem.
Date: Jan. 03, 2003
PubMed ID: 12435741
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