ZJE生物医学学术系列研讨会

主题: Histone phosphorylation recruits topoisomerase IIα to centromeres to safeguard genomic stability

主讲人: 汪方炜教授

Chromosome segregation in mitosis requires the removal of catenation between sister chromatids. Timely decatenation of sister DNAs at mitotic centromeres by topoisomerase IIα (TOP2A) is crucial to maintain genomic stability. The chromatin factors that recruit TOP2A to centromeres during mitosis remain unknown. Here, we show that histone phosphorylation is necessary and sufficient for the centromeric localization of TOP2A. We identify specific domains that are important for the phosphorylation-dependent localization of TOP2A at mitotic centromeres. Preventing TOP2A localization at centromeres interferes with sister chromatid disjunction, as evidenced by increased frequency of anaphase ultra-fine bridges (UFBs) that contain catenated DNA. Our study reveals a fundamental role for histone phosphorylation in resolving centromere DNA entanglements and safeguarding genomic stability during mitosis.