title: DNA damage-induced metaphase I arrest is mediated by the spindle assembly checkpoint and maternal age.
abstract: In mammalian oocytes DNA damage can cause chromosomal abnormalities that potentially lead to infertility and developmental disorders. However, there is little known about the response of oocytes to DNA damage. Here we find that oocytes with DNA damage arrest at metaphase of the first meiosis (MI). The MI arrest is induced by the spindle assembly checkpoint (SAC) because inhibiting the SAC overrides the DNA damage-induced MI arrest. Furthermore, this MI checkpoint is compromised in oocytes from aged mice. These data lead us to propose that the SAC is a major gatekeeper preventing the progression of oocytes harbouring DNA damage. The SAC therefore acts to integrate protection against both aneuploidy and DNA damage by preventing production of abnormal mature oocytes and subsequent embryos. Finally, we suggest escaping this DNA damage checkpoint in maternal ageing may be one of the causes of increased chromosome anomalies in oocytes and embryos from older mothers.
authors.affiliation: Department of Cell and Developmental Biology, Division of Biosciences, UCL, Gower Street, London WC1E 6BT, UK.|Department of Biological Applications and Technology, University of Ioannina, 45110 Ioannina, Greece.
authors.forename: Petros
authors.initials: P
authors.lastname: Marangos
authors.affiliation: Institute of Physiological Chemistry, Faculty of Medicine Carl Gustav Carus, Dresden University of Technology, Fiedlerstrasse 42, MTZ, 01307 Dresden, Germany.
authors.forename: Michelle
authors.initials: M
authors.lastname: Stevense
authors.affiliation: Department of Biological Applications and Technology, University of Ioannina, 45110 Ioannina, Greece.
authors.forename: Konstantina
authors.initials: K
authors.lastname: Niaka
authors.affiliation: Department of Biological Applications and Technology, University of Ioannina, 45110 Ioannina, Greece.
authors.forename: Michaela
authors.initials: M
authors.lastname: Lagoudaki
authors.affiliation: Department of Cell and Developmental Biology, Division of Biosciences, UCL, Gower Street, London WC1E 6BT, UK.
authors.forename: Ibtissem
authors.initials: I
authors.lastname: Nabti
authors.affiliation: Institute of Physiological Chemistry, Faculty of Medicine Carl Gustav Carus, Dresden University of Technology, Fiedlerstrasse 42, MTZ, 01307 Dresden, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Jessberger
authors.affiliation: Department of Cell and Developmental Biology, Division of Biosciences, UCL, Gower Street, London WC1E 6BT, UK.|Development and Stem Cells Program, Monash Biomedicine Discovery Institute and Department of Anatomy and Developmental Biology, Monash University, Melbourne, Victoria 3800, Australia.
authors.forename: John
authors.initials: J
authors.lastname: Carroll
mesh_terms: D000818:Animals; D004249:DNA Damage; D005260:Female; D059566:M Phase Cell Cycle Checkpoints; D008423:Maternal Age; D008540:Meiosis; D008677:Metaphase; D051379:Mice; D008810:Mice, Inbred C57BL; D009865:Oocytes / Q000166:cytology*; D011247:Pregnancy