Journal
EMBO JOURNAL
Volume 39, Issue 3, Pages -Publisher
WILEY
DOI: 10.15252/embj.2019101863
Keywords
Bub1; DNA decatenation; histone H2A phosphorylation; Sgo1; TOP2A
Categories
Funding
- National Natural Science Foundation of China (NSFC) [31571393]
- National Key Research and Development Program of China [2017YFA0503600]
- NSFC [31771499, 31322032, 31371359, 31561130155, 81702552]
- Natural Science Foundation of Zhejiang Province [LZ19C070001, LR13C070001]
- Royal Society Newton Advanced Fellowship [NA140075]
- Fundamental Research Funds for the Central Universities in China [2014XZZX003-35, 2018QN81011]
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Chromosome segregation in mitosis requires the removal of catenation between sister chromatids. Timely decatenation of sister DNAs at mitotic centromeres by topoisomerase II alpha (TOP2A) is crucial to maintain genomic stability. The chromatin factors that recruit TOP2A 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 TOP2A. Phosphorylation at residue-120 enhances histone H2A binding to TOP2A in vitro. The C-gate and the extreme C-terminal region are important for H2ApT120-dependent localization of TOP2A at centromeres. Preventing H2ApT120-mediated accumulation of TOP2A at mitotic centromeres interferes with sister chromatid disjunction, as evidenced by increased frequency of anaphase ultra-fine bridges (UFBs) that contain catenated DNA. Tethering TOP2A to centromeres bypasses the requirement for H2ApT120 in suppressing anaphase UFBs. These results demonstrate that H2ApT120 acts as a landmark that recruits TOP2A to mitotic centromeres to decatenate sister DNAs. Our study reveals a fundamental role for histone phosphorylation in resolving centromere DNA entanglements and safeguarding genomic stability during mitosis.
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