Cells in embryos and adult tissues have mechanisms that allow them to identify and respond to DNA damage, thereby ensuring that deleterious mutations cannot arise and persist in individuals. On page 3475, Keith Jones and colleagues investigate the mechanism by which mouse oocytes arrest upon DNA damage. This response involves activation of the spindle assembly checkpoint (SAC), which normally prevents the onset of anaphase until all chromosomes are correctly attached to the spindle. In this study, the authors find that, within minutes of DNA damage, SAC-associated proteins are not recruited to the sites of damage along chromosome arms, but instead become concentrated at the chromosome kinetochores, which act as a platform to generate the SAC signal. SAC activation is dependent on the activity of aurora kinase and MPS1 kinase but, interestingly, does not rely on PI3K-related kinases important for the DNA damage response in other systems. Furthermore, the authors show that the arrest response is unique to oocytes in meiosis I and does not occur in oocytes undertaking meiosis II. These results uncover a new mechanism by which DNA damage is dealt with in oocytes and provide clues into how the formation of genetically abnormal embryos is prevented.
