title: MutSα maintains the mismatch repair capability by inhibiting PCNA unloading.
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.
authors.affiliation: Graduate School of Science, Osaka University, Toyonaka, Japan.
authors.forename: Yoshitaka
authors.identifier: 0000-0003-0925-2004
authors.initials: Y
authors.lastname: Kawasoe
authors.affiliation: Department of Biology, Faculty of Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Toshiki
authors.identifier: 0000-0001-7597-2216
authors.initials: T
authors.lastname: Tsurimoto
authors.affiliation: Graduate School of Science, Osaka University, Toyonaka, Japan.
authors.forename: Takuro
authors.identifier: 0000-0003-3455-8224
authors.initials: T
authors.lastname: Nakagawa
authors.affiliation: Graduate School of Science, Osaka University, Toyonaka, Japan.
authors.forename: Hisao
authors.initials: H
authors.lastname: Masukata
authors.affiliation: Graduate School of Science, Osaka University, Toyonaka, Japan.
authors.forename: Tatsuro S
authors.identifier: 0000-0002-1947-7680
authors.initials: TS
authors.lastname: Takahashi
mesh_terms: D000818:Animals; D002457:Cell Extracts; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D053843:DNA Mismatch Repair; D051719:MutS DNA Mismatch-Binding Protein / Q000378:metabolism*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism*; D011485:Protein Binding; D014981:Xenopus; D015053:Zygote / Q000201:enzymology
chemical_list: D002457:Cell Extracts; D018809:Proliferating Cell Nuclear Antigen; D004247:DNA; D051719:MutS DNA Mismatch-Binding Protein
keywords: DNA replication; MutSα; Xenopus egg extract; biochemistry; chromosomes; genes; mismatch repair; proliferating cell nuclear antigen; xenopus