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Mol Cell. 2003 Nov;12(5):1077-86.

Mechanism of 5'-directed excision in human mismatch repair.

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  • 1Department of Biochemistry, Box 3711, Duke University Medical Center, Durham, NC 27710, USA.

Abstract

We have developed a purified system that supports mismatch-dependent 5'-->3' excision. In the presence of RPA, ATP, and a mismatch, MutSalpha activates 5'-->3' excision by EXOI, and excision terminates after removal of the mispair. MutSalpha confers high processivity on EXOI, and termination is due to RPA-dependent displacement of this processive complex from the helix and a weak ability of EXOI to reload at the RPA-bound gap in the product, as well as MutSalpha- and MutLalpha-dependent suppression of EXOI activity in the absence of a mismatch cofactor. As observed in the purified system, excision directed by a 5' strand break in HeLa nuclear extract can proceed in the absence of MutLalpha or PCNA, although 3' excision in the extract system requires both proteins.

PMID:
14636568
[PubMed - indexed for MEDLINE]
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