Cohesin Removal along the Chromosome Arms during the First Meiotic Division Depends on a NEK1-PP1γ-WAPL Axis in the Mouse
Year: 2016
Type: article
Abstract: Mammalian NIMA-like kinase-1 (NEK1) is a dual-specificity kinase highly expressed in mouse germ cells during prophase I of meiosis. Loss of NEK1 induces retention of cohesin on chromosomes at meiotic prophase I. Timely deposition and removal of cohesin is essential for accurate chromosome segregation. Two processes regulate cohesin removal: a non-proteolytic mechanism involving WAPL, sororin, and PDS5B and direct cleavage by separase. Here, we demonstrate a role for NEK1 in the regulation of WAPL loading during meiotic prophase I, via an interaction between NEK1 and PDS5B. This regulation of WAPL by NEK1-PDS5B is mediated by protein phosphatase 1 gamma (PP1γ), which both interacts with and is a phosphotarget of NEK1. Taken together, our results reveal that NEK1 phosphorylates PP1γ, leading to the dephosphorylation of WAPL, which, in turn, results in its retention on chromosome cores to promote loss of cohesion at the end of prophase I in mammals.
Source: Cell Reports
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,620
Awards: Reproductive Biology and Genomics Training Program, NIMA-like kinase NEK1 as a regulator of mammalian gametogenesis, G4635707143, Functional Analysis of the Dual Specificity Kinase NEK1 in Mammalian Meiosis, Genetic Pathways Effecting Crossover Control and Meiotic Recombination in Mammals, Small RNA Pathways in Mammalian Gametogenesis
OpenAlex ID: W2538401815