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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Elsevier
2016-10-01
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Series: | Cell Reports |
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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. |
first_indexed | 2024-12-10T08:41:35Z |
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id | doaj.art-59f47e0356ca4cd695b66652b9b3d798 |
institution | Directory Open Access Journal |
issn | 2211-1247 |
language | English |
last_indexed | 2024-12-10T08:41:35Z |
publishDate | 2016-10-01 |
publisher | Elsevier |
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series | Cell Reports |
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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