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In vitro reconstitution reveals requirement of Nek2a and cyclin A2 for Wapl-dependent removal of cohesin from prophase chromatin

Title data

Hellmuth, Susanne ; Stemmann, Olaf:
In vitro reconstitution reveals requirement of Nek2a and cyclin A2 for Wapl-dependent removal of cohesin from prophase chromatin.
bioRxiv , 2024
DOI: https://doi.org/10.1101/2024.03.12.584565

Official URL: Volltext

Project information

Project financing: Deutsche Forschungsgemeinschaft

Abstract in another language

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: Preprint, postprint
Refereed: No
Institutions of the University: Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Biology > Chair Genetics > Chair Genetics - Univ.-Prof. Dr. Olaf Stemmann
Result of work at the UBT: Yes
DDC Subjects: 500 Science > 570 Life sciences, biology
Date Deposited: 11 Apr 2024 07:56
Last Modified: 11 Apr 2024 07:56
URI: https://eref.uni-bayreuth.de/id/eprint/89293