The MutSalpha-proliferating cell nuclear antigen interaction in human DNA mismatch repair.

Journal Article (Journal Article)

We have examined the interaction parameters, conformation, and functional significance of the human MutSalpha(.) proliferating cell nuclear antigen (PCNA) complex in mismatch repair. The two proteins associate with a 1:1 stoichiometry and a K(D) of 0.7 microm in the absence or presence of heteroduplex DNA. PCNA does not influence the affinity of MutSalpha for a mismatch, and mismatch-bound MutSalpha binds PCNA. Small angle x-ray scattering studies have established the molecular parameters of the complex, which are consistent with an elongated conformation in which the two proteins associate in an end-to-end fashion in a manner that does not involve an extended unstructured tether, as has been proposed for yeast MutSalpha and PCNA ( Shell, S. S., Putnam, C. D., and Kolodner, R. D. (2007) Mol. Cell 26, 565-578 ). MutSalpha variants lacking the PCNA interaction motif are functional in 3'- or 5'-directed mismatch-provoked excision, but display a partial defect in 5'-directed mismatch repair. This finding is consistent with the modest mutability conferred by inactivation of the MutSalpha PCNA interaction motif and suggests that interaction of the replication clamp with other repair protein(s) accounts for the essential role of PCNA in MutSalpha-dependent mismatch repair.

Full Text

Duke Authors

Cited Authors

  • Iyer, RR; Pohlhaus, TJ; Chen, S; Hura, GL; Dzantiev, L; Beese, LS; Modrich, P

Published Date

  • May 9, 2008

Published In

Volume / Issue

  • 283 / 19

Start / End Page

  • 13310 - 13319

PubMed ID

  • 18326858

Pubmed Central ID

  • PMC2423938

International Standard Serial Number (ISSN)

  • 0021-9258

Digital Object Identifier (DOI)

  • 10.1074/jbc.M800606200


  • eng

Conference Location

  • United States