Age-dependent accumulation of RAD51 on non-damaged chromosomes prevents chromosome segregation in mammalian oocytes
Ito, M.; Soeda, S.; Kondo, T.; Furukohri, A.; Kajitani, M.; Ogata, R.; Ohsugi, M.; Shinohara, A.
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RAD51 is targeted to single-stranded (ss)DNA for homologous recombination and DNA replication fork homeostasis. However, the physiological consequences of RAD51 binding to intact double-stranded (ds)DNA, which is tightly limited in vivo, remain elusive. Here we revealed an intrinsic property of RAD51 to bind chromosome axes where cohesin and condensin bind, which is actively suppressed by FIGNL1 AAA+ ATPase. In Fignl1-deficient mouse oocytes, an age-dependent RAD51 accumulation with little DNA damage leads to improper chromosomal localization of condensin II and topoisomerase II, failure in chromosome condensation with massive chromosome entanglement, and meiosis I arrest. We propose that promiscuous RAD51 binding to non-damaged chromosomes, which is prevented by a RAD51 remodeler, is a unique type of chromosomal pathology associated with genome instability.
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