title: DNA damage induces a meiotic arrest in mouse oocytes mediated by the spindle assembly checkpoint.
abstract: Extensive damage to maternal DNA during meiosis causes infertility, birth defects and abortions. However, it is unknown if fully grown oocytes have a mechanism to prevent the creation of DNA-damaged embryos. Here we show that DNA damage activates a pathway involving the spindle assembly checkpoint (SAC) in response to chemically induced double strand breaks, UVB and ionizing radiation. DNA damage can occur either before or after nuclear envelope breakdown, and provides an effective block to anaphase-promoting complex activity, and consequently the formation of mature eggs. This contrasts with somatic cells, where DNA damage fails to affect mitotic progression. However, it uncovers a second function for the meiotic SAC, which in the context of detecting microtubule-kinetochore errors has hitherto been labelled as weak or ineffectual in mammalian oocytes. We propose that its essential role in the detection of DNA damage sheds new light on its biological purpose in mammalian female meiosis.
authors.affiliation: Centre for Biological Sciences, Faculty of Natural and Environmental Sciences, University of Southampton, Southampton SO17 1BJ, UK.
authors.forename: Josie K
authors.initials: JK
authors.lastname: Collins
authors.affiliation: Centre for Biological Sciences, Faculty of Natural and Environmental Sciences, University of Southampton, Southampton SO17 1BJ, UK.
authors.forename: Simon I R
authors.initials: SIR
authors.lastname: Lane
authors.affiliation: Centre for Biological Sciences, Faculty of Natural and Environmental Sciences, University of Southampton, Southampton SO17 1BJ, UK.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Merriman
authors.affiliation: Centre for Biological Sciences, Faculty of Natural and Environmental Sciences, University of Southampton, Southampton SO17 1BJ, UK.
authors.forename: Keith T
authors.identifier: http://orcid.org/0000-0002-0294-0851
authors.initials: KT
authors.lastname: Jones
mesh_terms: D000818:Animals; D059447:Cell Cycle Checkpoints; D004249:DNA Damage / Q000528:radiation effects; D005260:Female; D008540:Meiosis / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009865:Oocytes / Q000166:cytology* / Q000378:metabolism / Q000528:radiation effects; D008941:Spindle Apparatus / Q000378:metabolism* / Q000528:radiation effects; D014466:Ultraviolet Rays