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hMSH3 and hMSH6 interact with PCNA and colocalize with it to replication foci


Kleczkowska, H E; Marra, G; Lettieri, T; Jiricny, J (2001). hMSH3 and hMSH6 interact with PCNA and colocalize with it to replication foci. Genes and Development, 15(6):724-736.

Abstract

Proliferating cell nuclear antigen (PCNA) has been implicated in eukaryotic postreplicative mismatch correction, but the nature of its interaction with the repair machinery remained enigmatic. We now show that PCNA binds to the human mismatch binding factors hMutSalpha and hMutSbeta via their hMSH6 and hMSH3 subunits, respectively. The N-terminal domains of both proteins contain the highly conserved PCNA-binding motif Qxx[LI]xx[FF]. A variant of hMutSalpha, lacking this motif because of deletion of 77 N-terminal residues of the hMSH6 subunit, no longer was able to interact with PCNA in vitro and failed to restore mismatch repair in hMSH6-deficient cells. Colocalization of PCNA and hMSH6 or hMSH3 to replication foci implies an intimate link between replication and mismatch correction. We postulate that PCNA plays a role in repair initiation by guiding the mismatch repair proteins to free termini in the newly replicated DNA strands.

Proliferating cell nuclear antigen (PCNA) has been implicated in eukaryotic postreplicative mismatch correction, but the nature of its interaction with the repair machinery remained enigmatic. We now show that PCNA binds to the human mismatch binding factors hMutSalpha and hMutSbeta via their hMSH6 and hMSH3 subunits, respectively. The N-terminal domains of both proteins contain the highly conserved PCNA-binding motif Qxx[LI]xx[FF]. A variant of hMutSalpha, lacking this motif because of deletion of 77 N-terminal residues of the hMSH6 subunit, no longer was able to interact with PCNA in vitro and failed to restore mismatch repair in hMSH6-deficient cells. Colocalization of PCNA and hMSH6 or hMSH3 to replication foci implies an intimate link between replication and mismatch correction. We postulate that PCNA plays a role in repair initiation by guiding the mismatch repair proteins to free termini in the newly replicated DNA strands.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Molecular Cancer Research
07 Faculty of Science > Institute of Molecular Cancer Research
Dewey Decimal Classification:570 Life sciences; biology
Language:English
Date:2001
Deposited On:09 Jul 2010 13:19
Last Modified:05 Apr 2016 14:09
Publisher:Cold Spring Harbor Laboratory Press
ISSN:0890-9369
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:10.1101/gad.191201
PubMed ID:11274057
Permanent URL: http://doi.org/10.5167/uzh-34463

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