Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.celrep.2017.10.032

Other Link： https://www.sciencedirect.com/science/article/pii/S221112471731464X?via%3Dihub

Language：English   Publishing type：Research paper (scientific journal)  

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, MutS a 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 MutS a in the retention of the post-replicative MMR capability.

DOI： 10.7554/eLife.15155

Other Link： https://elifesciences.org/articles/15155

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1111/febs.12344

Other Link： https://febs.onlinelibrary.wiley.com/doi/full/10.1111/febs.12344

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Cold Spring Harbor Laboratory  

Abstract

UHRF1-dependent ubiquitin signaling plays an integral role in the regulation of maintenance DNA methylation. UHRF1 catalyzes transient dual mono-ubiquitylation of PAF15 (PAF15Ub2), which regulates the localization and activation of DNMT1 at DNA methylation sites during DNA replication. Although the initiation of UHRF1-mediated PAF15 ubiquitin signaling has been relatively well characterized, mechanisms underlying its termination and how they are coordinated with the completion of maintenance DNA methylation have not yet been clarified. This study shows that deubiquitylation by USP7 and unloading by ATAD5 (ELG1 in yeast) are pivotal processes for the removal of PAF15 from chromatin. On replicating chromatin, USP7 specifically interacts with PAF15Ub2 in a complex with DNMT1. USP7 depletion or inhibition of the interaction between USP7 and PAF15 results in abnormal accumulation of PAF15Ub2 on chromatin. Furthermore, we also find that the non-ubiquitylated form of PAF15 (PAF15Ub0) is removed from chromatin in an ATAD5-dependent manner. PAF15Ub2 was retained at high levels on chromatin when the catalytic activity of DNMT1 was inhibited, suggesting that the completion of maintenance DNA methylation is essential for termination of UHRF1-mediated ubiquitin signaling. This finding provides a molecular understanding of how the maintenance DNA methylation machinery is disassembled at the end of the S phase.

DOI： 10.7554/eLife.79013

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Event date： 2021.11 - 2021.12

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：千葉県千葉市   Country：Japan  

Event date： 2021.10

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：オンライン開催   Country：Japan  

Event date： 2021.1

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：オンライン   Country：Other  

Event date： 2019.12

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：福岡県福岡市   Country：Other  

Event date： 2018.12

Language：English   Presentation type：Oral presentation (general)  

Venue：愛知県名古屋市   Country：Japan  

Event date： 2018.11

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：神奈川県横浜市   Country：Other  

Event date： 2014.11

Language：English   Presentation type：Oral presentation (general)  

Venue：静岡県御殿場市   Country：Other  

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：静岡県焼津市   Country：Other  

Language：Japanese   Presentation type：Oral presentation (general)  

Country：Other  

PCNA plays a key role in identification of the newly synthesized DNA strand in eukaryotic mismatch repair

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：福岡県福岡市   Country：Other  

Language：English   Presentation type：Oral presentation (general)  

Country：Other  

Orientation of PCNA loading determines the strand specificity of the eukaryotic mismatch repair reaction

Language：English   Presentation type：Oral presentation (general)  

Country：Other  

Evidence that DNA-loaded PCNA acts as the strand marker for eukaryotic mismatch repair

Language：Japanese  

Venue：神奈川県横浜市   Country：Other