Back to Search Start Over

Mechanism of 5′-Directed Excision in Human Mismatch Repair

Authors :
Jochen Genschel
Paul Modrich
Source :
Molecular Cell. 12(5):1077-1086
Publication Year :
2003
Publisher :
Elsevier BV, 2003.

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.

Details

ISSN :
10972765
Volume :
12
Issue :
5
Database :
OpenAIRE
Journal :
Molecular Cell
Accession number :
edsair.doi.dedup.....000e8a1f1761fae35d7253e91a67f3ea
Full Text :
https://doi.org/10.1016/s1097-2765(03)00428-3