ArticleeLife2023
The termination of UHRF1-dependent PAF15 ubiquitin signaling is regulated by USP7 and ATAD5.
Article in eLife, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 17 citations in OpenAlex.
- DAXX promotes SUMOylation of chromatin-trapped DNMT1.Journal of biochemistry · 2026Article
- Mechanisms of USP7/MAGEL2 Complex Assembly and Its Mutational Disruption in Neurodevelopmental Diseases.bioRxiv : the preprint server for biology · 2026Article
- USP4 promotes non-small cell lung cancer tumorigenesis by antagonizing CNOT4-mediated degradation of PAF1.Respiratory research · 2026Article
- USP7 deubiquitinase stabilizes FAN1 to support DNA crosslink repair and suppress CAG repeat expansion.Nature communications · 2026Article
- Cryo-EM reveals evolutionarily conserved and distinct structural features of plant CG maintenance methyltransferase MET1.Nature communications · 2025Article
- The human ATAD5 has evolved unique structural elements to function exclusively as a PCNA unloader.Nature structural & molecular biology · 2024Article
- Structure of human DPPA3 bound to the UHRF1 PHD finger reveals its functional and structural differences from mouse DPPA3.Communications biology · 2024Article
- The Atad5 RFC-like complex is the major unloader of proliferating cell nuclear antigen in Xenopus egg extracts.The Journal of biological chemistry · 2024Article
- Mechanistic insights into UHRF1‑mediated DNA methylation by structure‑based functional clarification of UHRF1 domains (Review).Oncology letters · 2023Review
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Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
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, the 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 the 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.
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