PCNA recruits cohesin loader Scc2 to ensure sister chromatid cohesion
Open accessPublished version of a preprint
Abstract
Sister chromatid cohesion, established during replication by the ring-shaped multiprotein complex cohesin, is essential for faithful chromosome segregation. Replisome-associated proteins are required to generate cohesion by two independent pathways. One mediates conversion of cohesins bound to unreplicated DNA ahead of replication forks into cohesive entities behind them, while the second promotes cohesin de novo loading onto newly replicated DNA. The latter process depends on the cohesin loader Scc2 (NIPBL in vertebrates) and the alternative PCNA loader CTF18-RFC. However, the mechanism of de novo cohesin loading during replication is unknown. Here we show that PCNA physically recruits the yeast cohesin loader Scc2 via its C-terminal PCNA-interacting protein motif. Binding to PCNA is crucial, as the scc2-pip mutant deficient in Scc2–PCNA interaction is defective in cohesion when combined with replisome mutants of the cohesin conversion pathway. Importantly, the role of NIPBL recruitment to PCNA for cohesion generation is conserved in vertebrate cells.
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Cites
Highly accurate protein structure prediction with AlphaFold
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- Authors
- Psakhye, I., Kawasumi, R., Abe, T., Hirota, K., & Branzei, D.
- Affiliations
- IFOM (IT)
- Tokyo Metropolitan University (JP)
- Corresponding author
- Psakhye, Ivan
- Branzei, Dana
- Venue
- Nature Structural & Molecular Biology
- Published
- 2023-08-17
- Volume
- 30
- Issue
- 9
- Pages
- 1286-1294
- ISSN
- 1545-9985 (ISSN-L)
- 1545-9993
- PMC
- PMC10497406
- OpenAlex
- W4385948983
- Cited by
- 23
- References
- 5
- Citations by year
- 2026: 4 · 2025: 11 · 2024: 6 · 2023: 1 · 2022: 1
- FWCI
- 1.95
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Nature Structural & Molecular Biology (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Universitätsbibliographie, Universität Duisburg-Essen (submittedVersion)
- CNR ExploRA (submittedVersion)
- Funders
- Takeda Science Foundation
- Novartis Foundation
- Uehara Memorial Foundation
- Tokyo Metropolitan Institute of Medical Science
- Tokyo Metropolitan Government
- University of Oxford
- Fondazione Umberto Veronesi
- Associazione Italiana per la Ricerca sul Cancro (IG 18976, 23710, 682190, ALTF 561-2014, IG 23710, Rif.22403, 18976)
- Max-Planck-Institut für Bildungsforschung
- Japan Society for the Promotion of Science (22K15040, 22H05072, 21K19235, 19KK0210, 20H04337, 20K06760)
- H2020 European Research Council (682190)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- sister chromatid cohesion, PCNA, replisome, NIPBL, chromosome segregation, DNA replication, Saccharomyces cerevisiae
- MeSH terms
- Cohesins, Animals, Chromatids, Saccharomyces cerevisiae, Cell Cycle Proteins, Proliferating Cell Nuclear Antigen, Chromosome Segregation
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