Preimplantation mouse embryos depend on inhibitory phosphorylation of separase to prevent chromosome missegregation.

Molecular and Cellular Biology
Xingxu HuangP Zhang

Abstract

Separase is a critical protease that catalyzes the cleavage of sister chromatid cohesins to allow the separation of sister chromatids in the anaphase. Its activity must be inhibited prior to the onset of the anaphase. Two inhibitory mechanisms exist in vertebrates that block the protease activity. One mechanism is through binding and inhibition by securin, and another is phosphorylation on Ser1126 (in humans [Ser1121 in mice]). These two mechanisms are largely redundant. However, phosphorylation on Ser1121 is critical for the prevention of premature sister separation in embryonic germ cells. As a result, Ser1121-to-Ala mutation leads to depletion of germ cells in development and subsequently to infertility in mice. Here, we report that the same mutation also causes embryogenesis failure between the 8- and 16-cell stages in mice. Our results indicate a critical role of separase phosphorylation in germ cell development as well as in early embryogenesis. Thus, deregulation of separase may be a significant contributor to infertility in humans.

References

Dec 3, 1999·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·G FangM W Kirschner
May 10, 2000·Current Opinion in Cell Biology·D E Koshland, V Guacci
Aug 10, 2000·Trends in Cell Biology·K J Dej, T L Orr-Weaver
Jan 11, 2001·Chromosoma·J Wolstenholme, R R Angell
Apr 3, 2001·Nature Reviews. Genetics·T Hassold, P Hunt
Jul 11, 2001·Novartis Foundation Symposium·K NasmythF Uhlmann
Dec 19, 2001·Cell·O StemmannM W Kirschner
Mar 22, 2002·Nature Reviews. Cancer·P V Jallepalli, C Lengauer
Apr 5, 2002·Molecular Cell·Izabela SumaraJan-Michael Peters
Jun 7, 2002·Molecular Cell·Jan-Michael Peters
Jul 10, 2004·Current Biology : CB·Juan F Giménez-AbiánJan-Michael Peters
Sep 2, 2004·Nature Reviews. Molecular Cell Biology·Boris Zhivotovsky, Guido Kroemer
Jun 15, 2005·Annual Review of Biochemistry·Kim Nasmyth, Christian H Haering
Jul 2, 2005·Molecular Cell·Ingo H GorrOlaf Stemmann
Oct 1, 2005·Nature Reviews. Cancer·Geert J P L KopsDon W Cleveland
Mar 15, 2006·The Journal of Cell Biology·Karin G WirthKim Nasmyth
Mar 17, 2006·Nature·Tomoya S KitajimaYoshinori Watanabe
Feb 28, 2007·Molecular and Cellular Biology·Min LiPumin Zhang
Oct 4, 2007·Human Molecular Genetics·Terry HassoldPatricia Hunt

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Citations

Nov 6, 2009·Annual Review of Genetics·Kim Nasmyth, Christian H Haering
Jun 2, 2012·Reproduction : the Official Journal of the Society for the Study of Fertility·D McBrideM Clinton
Apr 19, 2011·Seminars in Cell & Developmental Biology·Hui Zou
Feb 18, 2011·Nucleus·Martin Kucej, Hui Zou
Aug 28, 2016·Trends in Cell Biology·Julia Kamenz, Silke Hauf
May 2, 2014·The EMBO Journal·Susanne HellmuthOlaf Stemmann
Apr 11, 2020·Scientific Reports·Pan Young JeongJoel H Rothman
Aug 4, 2012·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Yael PomerantzNava Dekel
Feb 11, 2015·The Journal of Biological Chemistry·Susanne HellmuthOlaf Stemmann
Aug 28, 2021·International Journal of Molecular Sciences·Martin AngerMarketa Charousova

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