MutSα maintains the mismatch repair capability by inhibiting PCNA unloading

Yoshitaka Kawasoe, Toshiki Tsurimoto, Takuro Nakagawa, Hisao Masukata, Tatsuro S. Takahashi

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)

Abstract

Eukaryotic mismatch repair (MMR) utilizes single-strand breaks as signals to target the strand to be repaired. DNA-bound PCNA is also presumed to direct MMR. The MMR capability must be limited to a post-replicative temporal window during which the signals are available. However, both identity of the signal(s) involved in the retention of this temporal window and the mechanism that maintains the MMR capability after DNA synthesis remain unclear. Using Xenopus egg extracts, we discovered a mechanism that ensures long-term retention of the MMR capability. We show that DNA-bound PCNA induces strand-specific MMR in the absence of strand discontinuities. Strikingly, MutSα inhibited PCNA unloading through its PCNA-interacting motif, thereby extending significantly the temporal window permissive to strand-specific MMR. Our data identify DNA-bound PCNA as the signal that enables strand discrimination after the disappearance of strand discontinuities, and uncover a novel role of MutSα in the retention of the post-replicative MMR capability.

Original languageEnglish
Article numbere15155
JournaleLife
Volume5
Issue number2016JULY
DOIs
Publication statusPublished - Jul 12 2016

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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