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URN to cite this document: urn:nbn:de:bvb:703-epub-8693-5
Title data
Hellmuth, Susanne ; Stemmann, Olaf:
Requirement of Nek2a and cyclin A2 for Wapl-dependent removal of cohesin from prophase chromatin.
In: The EMBO Journal.
Vol. 43
(2024)
Issue 21
.
- pp. 5237-5259.
ISSN 1460-2075
DOI der Verlagsversion: https://doi.org/10.1038/s44318-024-00228-9
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Project information
| Project title: |
Project's official title Project's id Aufhebung der Schwesterchromatid-Kohäsion in der Mitose: Die Rolle von Phosphorylierung und Deacetylierung 450806808 Open Access Publizieren No information |
|---|---|
| Project financing: |
Deutsche Forschungsgemeinschaft |
Abstract
Sister chromatid cohesion is mediated by the cohesin complex. In mitotic prophase cohesin is removed from chromosome arms in a Wapl- and phosphorylation-dependent manner. Sgo1-PP2A protects pericentromeric cohesion by dephosphorylation of cohesin and its associated Wapl antagonist sororin. However, Sgo1-PP2A relocates to inner kinetochores well before sister chromatids are separated by separase, leaving pericentromeric regions unprotected. Why deprotected cohesin is not removed by Wapl remains enigmatic. By reconstituting Wapl-dependent cohesin removal from chromatin in vitro, we discovered a requirement for Nek2a and Cdk1/2-cyclin A2. These kinases phosphorylate cohesin-bound Pds5b, thereby converting it from a sororin- to a Wapl- interactor. Replacement of endogenous Pds5b by a phosphorylation mimetic variant causes premature sister chromatid separation (PCS). Conversely, phosphorylation- resistant Pds5b impairs chromosome arm separation in prometaphase-arrested cells and suppresses PCS in the absence of Sgo1. Early mitotic degradation of Nek2a and cyclin A2 may therefore explain why only separase, but not Wapl, can trigger anaphase.
Further data
| Item Type: | Article in a journal |
|---|---|
| DDC Subjects: | 500 Science > 570 Life sciences, biology |
| Institutions of the University: | Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Biology > Chair Genetics > Chair Genetics - Univ.-Prof. Dr. Olaf Stemmann Faculties Faculties > Faculty of Biology, Chemistry and Earth Sciences Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Biology Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Biology > Chair Genetics |
| Language: | English |
| Originates at UBT: | Yes |
| URN: | urn:nbn:de:bvb:703-epub-8693-5 |
| Date Deposited: | 27 Nov 2025 10:23 |
| Last Modified: | 27 Nov 2025 10:26 |
| URI: | https://epub.uni-bayreuth.de/id/eprint/8693 |
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