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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Genschel, J; Modrich, P

Published Date

  • November 2003

Published In

Volume / Issue

  • 12 / 5

Start / End Page

  • 1077 - 1086

PubMed ID

  • 14636568

Pubmed Central ID

  • 14636568

Electronic International Standard Serial Number (EISSN)

  • 1097-4164

International Standard Serial Number (ISSN)

  • 1097-2765

Digital Object Identifier (DOI)

  • 10.1016/s1097-2765(03)00428-3

Language

  • eng