論文

基本情報

氏名 河野 真二
氏名(カナ) カワノ シンジ
氏名(英語) Kawano Shinji
所属 生命科学部 生物科学科
職名 准教授
researchmap研究者コード B000335013
researchmap機関 岡山理科大学

題名

Role of the Topoisomerase IIα Chromatin Tether domain in Nucleosome Binding & Chromosome Segregation

単著・共著の別

著者

Sanjana Sundararajan, Hyewon Park, Shinji Kawano, Marnie Johansson, Tomoko Saito-Fujita, Noriko Saitoh, Alexei Arnaoutov, Mary Dasso, Duncan J. Clarke, Yoshiaki Azuma

概要

Due to the intrinsic nature of DNA replication, replicated genomes retain catenated genomic loci that must be resolved to ensure faithful segregation of sister chromatids in mitosis. Type II DNA Topoisomerase (TopoII) decatenates the catenated genomic DNA through its unique Strand Passage Reaction (SPR). Loss of SPR activity results in anaphase chromosome bridges and formation of Polo-like Kinase Interacting Checkpoint Helicase (PICH)-coated ultra-fine DNA bridges (UFBs) whose timely resolution is required to prevent micronuclei formation. Vertebrates have two TopoII isoforms– TopoIIα and TopoIIβ, that share a conserved catalytic core. However, the essential mitotic function of TopoIIα cannot be compensated by TopoIIβ, due to differences in their catalytically inert C-terminal domains (CTDs). Using genome-edited human cells, we show that specific binding of TopoIIα to methylated histone, tri-methylated H3K27 (H3K27me3), via its Chromatin Tether (ChT) domain within the CTD contributes critically to avoid anaphase UFB formation. Reducing H3K27 methylation prior to mitosis increases UFBs, revealing a requirement for proper establishment of H3K27me3 after DNA replication to facilitate TopoIIα-ChT dependent UFB prevention. We propose that interaction of the TopoIIα-ChT with H3K27me3 is a key factor that ensures the complete resolution of catenated loci to permit faithful chromosome segregation in human cells.

発表雑誌等の名称

bioRχiv

出版者

開始ページ

終了ページ

発行又は発表の年月

2021/10

査読の有無

無し

招待の有無

無し

記述言語

掲載種別

ISSN

ID:DOI

https://doi.org/10.1101/2021.10.03.462934

ID:NAID(CiNiiのID)

ID:PMID

URL

JGlobalID

arXiv ID

ORCIDのPut Code

DBLP ID