Cohesin Removal along the Chromosome Arms during the First Meiotic Division Depends on a NEK1-PP1γ-WAPL Axis in the Mouse

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 segregatio...

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Main Authors: Miguel A. Brieño-Enríquez, Stefannie L. Moak, Melissa Toledo, Joshua J. Filter, Stephen Gray, José L. Barbero, Paula E. Cohen, J. Kim Holloway
Format: Article
Language:English
Published: Elsevier 2016-10-01
Series:Cell Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124716313158
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author Miguel A. Brieño-Enríquez
Stefannie L. Moak
Melissa Toledo
Joshua J. Filter
Stephen Gray
José L. Barbero
Paula E. Cohen
J. Kim Holloway
author_facet Miguel A. Brieño-Enríquez
Stefannie L. Moak
Melissa Toledo
Joshua J. Filter
Stephen Gray
José L. Barbero
Paula E. Cohen
J. Kim Holloway
author_sort Miguel A. Brieño-Enríquez
collection DOAJ
description 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.
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spelling doaj.art-59f47e0356ca4cd695b66652b9b3d7982022-12-22T01:55:51ZengElsevierCell Reports2211-12472016-10-0117497798610.1016/j.celrep.2016.09.059Cohesin Removal along the Chromosome Arms during the First Meiotic Division Depends on a NEK1-PP1γ-WAPL Axis in the MouseMiguel A. Brieño-Enríquez0Stefannie L. Moak1Melissa Toledo2Joshua J. Filter3Stephen Gray4José L. Barbero5Paula E. Cohen6J. Kim Holloway7Department of Biomedical Sciences and Center for Reproductive Genomics, Cornell University, Ithaca, NY 14853, USADepartment of Biomedical Sciences and Center for Reproductive Genomics, Cornell University, Ithaca, NY 14853, USADepartment of Biomedical Sciences and Center for Reproductive Genomics, Cornell University, Ithaca, NY 14853, USADepartment of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USADepartment of Biomedical Sciences and Center for Reproductive Genomics, Cornell University, Ithaca, NY 14853, USADepartment of Cellular and Molecular Biology, Laboratory of Chromosomal Dynamics in Meiosis, Centro de Investigaciones Biológicas (CSIC), Madrid 28040, SpainDepartment of Biomedical Sciences and Center for Reproductive Genomics, Cornell University, Ithaca, NY 14853, USADepartment of Biomedical Sciences and Center for Reproductive Genomics, Cornell University, Ithaca, NY 14853, USAMammalian 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.http://www.sciencedirect.com/science/article/pii/S2211124716313158meiosiscohesinmouseNIMA-like kinaseWAPLprophase pathway
spellingShingle Miguel A. Brieño-Enríquez
Stefannie L. Moak
Melissa Toledo
Joshua J. Filter
Stephen Gray
José L. Barbero
Paula E. Cohen
J. Kim Holloway
Cohesin Removal along the Chromosome Arms during the First Meiotic Division Depends on a NEK1-PP1γ-WAPL Axis in the Mouse
Cell Reports
meiosis
cohesin
mouse
NIMA-like kinase
WAPL
prophase pathway
title Cohesin Removal along the Chromosome Arms during the First Meiotic Division Depends on a NEK1-PP1γ-WAPL Axis in the Mouse
title_full Cohesin Removal along the Chromosome Arms during the First Meiotic Division Depends on a NEK1-PP1γ-WAPL Axis in the Mouse
title_fullStr Cohesin Removal along the Chromosome Arms during the First Meiotic Division Depends on a NEK1-PP1γ-WAPL Axis in the Mouse
title_full_unstemmed Cohesin Removal along the Chromosome Arms during the First Meiotic Division Depends on a NEK1-PP1γ-WAPL Axis in the Mouse
title_short Cohesin Removal along the Chromosome Arms during the First Meiotic Division Depends on a NEK1-PP1γ-WAPL Axis in the Mouse
title_sort cohesin removal along the chromosome arms during the first meiotic division depends on a nek1 pp1γ wapl axis in the mouse
topic meiosis
cohesin
mouse
NIMA-like kinase
WAPL
prophase pathway
url http://www.sciencedirect.com/science/article/pii/S2211124716313158
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