Geminin deletion in mouse oocytes results in impaired embryo development and reduced fertility

Molecular Biology of the Cell
Xue-Shan MaQing-Yuan Sun

Abstract

Geminin controls proper centrosome duplication, cell division, and differentiation. We investigated the function of geminin in oogenesis, fertilization, and early embryo development by deleting the geminin gene in oocytes from the primordial follicle stage. Oocyte-specific disruption of geminin results in low fertility in mice. Even though there was no evident anomaly of oogenesis, oocyte meiotic maturation, natural ovulation, or fertilization, early embryo development and implantation were impaired. The fertilized eggs derived from mutant mice showed developmental delay, and many were blocked at the late zygote stage. Cdt1 protein was decreased, whereas Chk1 and H2AX phosphorylation was increased, in fertilized eggs after geminin depletion. Our results suggest that disruption of maternal geminin may decrease Cdt1 expression and cause DNA rereplication, which then activates the cell cycle checkpoint and DNA damage repair and thus impairs early embryo development.

References

Jul 11, 1998·Cell·T J McGarry, M W Kirschner
Dec 23, 2000·Science·J A WohlschlegelA Dutta
Sep 26, 2001·The Journal of Biological Chemistry·S BurmaD J Chen
Oct 24, 2001·The Journal of Biological Chemistry·I M Ward, J Chen
Oct 22, 2002·Molecular Biology of the Cell·Thomas J McGarry
Feb 20, 2004·Nature·Filippo Del BeneJoachim Wittbrodt
Aug 17, 2004·The Journal of Biological Chemistry·Jacqueline M BenjaminThomas J McGarry
Sep 24, 2004·Biology of Reproduction·Martin AngerRichard M Schultz
Jul 19, 2005·Genes & Development·Seongjin SeoKristen L Kroll
Oct 24, 2006·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Kentaro HaraKeiko Nakayama
Dec 21, 2006·The Journal of Biological Chemistry·Sarah L KernsThomas J McGarry
May 9, 2007·Frontiers in Bioscience : a Journal and Virtual Library·Kenichi Yoshida
Aug 25, 2007·The Journal of Biological Chemistry·Jie Jessie Lin, Anindya Dutta
Aug 12, 2008·The Journal of Biological Chemistry·Lova RakotomalalaOurania Andrisani
Aug 7, 2009·The Journal of Biological Chemistry·Yadushyla Narasimhachar, Martine Coué
Nov 3, 2010·The Journal of Clinical Investigation·Kathryn M ShinnickThomas J McGarry
Mar 1, 2012·Journal of Cell Science·Kathleen Klotz-NoackJ Julian Blow
May 23, 2012·Proceedings of the National Academy of Sciences of the United States of America·Bo ZhouGuang Zhu
Aug 18, 2012·Developmental Biology·Kelly A BarryThomas J McGarry
Sep 27, 2013·PloS One·Golnaz A TabriziMichael Kessel

❮ Previous
Next ❯

Citations

Jul 12, 2017·The Journal of Reproduction and Development·Yue YuanQing-Yuan Sun
Nov 20, 2019·The FEBS Journal·Hashim AliMauro Giacca
Aug 30, 2018·Cell Death and Differentiation·Lin HuangQing-Yuan Sun
May 26, 2020·Developmental Biology·Emily M A LewisKristen L Kroll

❮ Previous
Next ❯

Methods Mentioned

BETA
PCR
gene knockout

Related Concepts

Related Feeds

Cell Checkpoints & Regulators

Cell cycle checkpoints are a series of complex checkpoint mechanisms that detect DNA abnormalities and ensure that DNA replication and repair are complete before cell division. They are primarily regulated by cyclins, cyclin-dependent kinases, and the anaphase-promoting complex/cyclosome. Here is the latest research.