Premium
Histone H2A phosphorylation recruits topoisomerase II α to centromeres to safeguard genomic stability
Author(s) -
Zhang Miao,
Liang Cai,
Chen Qinfu,
Yan Haiyan,
Xu Junfen,
Zhao Hongxia,
Yuan Xueying,
Liu Jingbo,
Lin Shixian,
Lu Weiguo,
Wang Fangwei
Publication year - 2019
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.2019101863
Subject(s) - biology , centromere , histone , topoisomerase , histone h3 , genetics , phosphorylation , safeguard , histone h2a , dna , microbiology and biotechnology , gene , chromosome , political science , law
Chromosome segregation in mitosis requires the removal of catenation between sister chromatids. Timely decatenation of sister DNA s at mitotic centromeres by topoisomerase II α ( TOP 2A) is crucial to maintain genomic stability. The chromatin factors that recruit TOP 2A to centromeres during mitosis remain unknown. Here, we show that histone H2A Thr‐120 phosphorylation (H2ApT120), a modification generated by the mitotic kinase Bub1, is necessary and sufficient for the centromeric localization of TOP 2A. Phosphorylation at residue‐120 enhances histone H2A binding to TOP 2A in vitro . The C‐gate and the extreme C‐terminal region are important for H2ApT120‐dependent localization of TOP 2A at centromeres. Preventing H2ApT120‐mediated accumulation of TOP 2A at mitotic centromeres interferes with sister chromatid disjunction, as evidenced by increased frequency of anaphase ultra‐fine bridges ( UFB s) that contain catenated DNA . Tethering TOP 2A to centromeres bypasses the requirement for H2ApT120 in suppressing anaphase UFB s. These results demonstrate that H2ApT120 acts as a landmark that recruits TOP 2A to mitotic centromeres to decatenate sister DNA s. Our study reveals a fundamental role for histone phosphorylation in resolving centromere DNA entanglements and safeguarding genomic stability during mitosis.