TP53BP1 Regulates Chromosome Alignment and Spindle Bipolarity by Controlling MTOCs during Meiosis in Oocytes

Meiotic oocytes lack classic centrosomes; therefore, bipolar-spindle assembly depends on the clustering of acentriolar microtubule-organizing centers (MTOCs) into two poles. Tumor suppressor P53-binding protein 1 (TP53BP1) is a known mediator in DNA damage response. Recent studies have revealed a new role of TP53BP1 in maintaining centrosome integrity in mitosis. However, the role of TP53BP1 in oocyte meiosis is unclear. Our results show that TP53BP1 participates in DNA damage responses in oocyte, as well as stablishment of chromosome alignment and spindle bipolarity by controlling the clustering of MTOCs during oocyte maturation. TP53BP1 was localized in the cytoplasm and concentrated around the spindle/chromosome region. Knockdown of TP53BP1 induced abnormal DNA damage response involving RAD51 and formation of γH2AX foci. TP53BP1 was also required for the clustering of MTOCs into two spindle poles during pro-meiosis I. Deletion of TP53BP1 induced perturbation in MTOC-localized Aurora Kinase A (AURKA). The knockdown of TP53BP1 induced microtubules to dis-attach from the kinetochores and increased the rate of aneuploidy. Taken together, our data show that TP53BP1 plays crucial roles in chromosome stability and spindle bipolarity during meiotic maturation by regulating the clustering of MTOCs.