Reduced MAD2 levels dampen the apoptotic response to non-exchange sex chromosomes and lead to sperm aneuploidy

Development
Imrul Faisal, Liisa Kauppi

Abstract

In meiosis, non-exchange homologous chromosomes are at risk for mis-segregation and should be monitored by the spindle assembly checkpoint (SAC) to avoid formation of aneuploid gametes. Sex chromosome mis-segregation is particularly common and can lead to sterility or to aneuploid offspring (e.g. individuals with Turner or Klinefelter syndrome). Despite major implications for health and reproduction, modifiers of meiotic SAC robustness and the subsequent apoptotic response in male mammals remain obscure. Levels of SAC proteins, e.g. MAD2, are crucial for normal checkpoint function in many experimental systems, but surprisingly, apparently not in male meiosis, as indicated by the lack of chromosome segregation defects reported earlier in Mad2+/- spermatocytes. To directly test whether MAD2 levels impact the meiotic response to mis-segregating chromosomes, we used Spo11β-onlymb mice that are prone to non-exchange X-Y chromosomes. We show that reduced MAD2 levels attenuate the apoptotic response to mis-segregating sex chromosomes and allow the formation of aneuploid sperm. These findings demonstrate that SAC protein levels are crucial for the efficient elimination of aberrant spermatocytes.

References

Aug 9, 1991·Cell·R Li, A W Murray
Oct 1, 1991·Molecular Reproduction and Development·M J SutcliffeP S Burgoyne
Jan 18, 1994·Proceedings of the National Academy of Sciences of the United States of America·T AshleyD C Ward
Jun 28, 1996·Cell·W EdelmannR Kucherlapati
Oct 27, 1999·Genomics·P J Romanienko, R D Camerini-Otero
Oct 20, 2000·European Journal of Human Genetics : EJHG·N S ThomasP A Jacobs
Apr 3, 2001·Nature Reviews. Genetics·T Hassold, P Hunt
Nov 3, 2001·Genome Research·J PerryA Ashworth
Aug 21, 2003·Human Reproduction Update·N S Thomas, T J Hassold
Nov 15, 2003·Current Biology : CB·Marion A ShonnAndrew W Murray
Jun 23, 2004·Nature Genetics·Darren J BakerJan M van Deursen
May 2, 2006·Current Opinion in Genetics & Development·Heather HallTerry Hassold
Jul 22, 2006·Biochemical Society Transactions·K B Jeganathan, J M van Deursen
Dec 27, 2006·Cancer Cell·Rocío SotilloRobert Benezra
Aug 31, 2007·Human Molecular Genetics·Kyle A FergusonSai Ma
May 20, 2011·Molecular Biology of the Cell·Erin L BarnhartScott C Schuyler
Nov 17, 2011·Human Reproduction Update·Shao-Chen Sun, Nam-Hyung Kim
May 4, 2012·Proceedings of the National Academy of Sciences of the United States of America·Agnieszka KolanoMarie-Hélène Verlhac
Sep 8, 2012·Annals of the New York Academy of Sciences·Liisa KauppiScott Keeney
Nov 24, 2012·Current Biology : CB·Pablo Lara-GonzalezStephen S Taylor
Oct 8, 2013·Nature Cell Biology·Philippe CollinJonathon Pines
Apr 22, 2015·Nature Communications·Sandra A TouatiKatja Wassmann

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Citations

Dec 20, 2018·Cellular and Molecular Life Sciences : CMLS·Simon Lane, Liisa Kauppi

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