서울시 서초구 반포대로 222 가톨릭대학교 성의교정 / TEL : 02-2258-7114 / FAX : 02-532-6537

222 Banpo-daero Seocho-gu, Seoul, (06591) Republic of korea / TEL : +82-2-2258-7114 / FAX : +82-2-532-6537

oncogenomics lab
2018년 3월 2일

김정규 박사, 한빛사 논문 등극 (Mol. Cell 2017)

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Mol. Cell, Available online 14 December 2017 | https://doi.org/10.1016/j.molcel.2017.11.021

Replication Stress Shapes a Protective Chromatin Environment across Fragile Genomic Regions

 Authors and Affiliations

Abstract Recent integrative epigenome analyses highlight the importance of functionally distinct chromatin states for accurate cell function. How these states are established and maintained is a matter of intense investigation. Here, we present evidence for DNA damage as an unexpected means to shape a protective chromatin environment at regions of recurrent replication stress (RS). Upon aberrant fork stalling, DNA damage signaling and concomitant H2AX phosphorylation coordinate the FACT-dependent deposition of macroH2A1.2, a histone variant that promotes DNA repair by homologous recombination (HR). MacroH2A1.2, in turn, facilitates the accumulation of the tumor suppressor and HR effector BRCA1 at replication forks to protect from RS-induced DNA damage. Consequently, replicating primary cells steadily accrue macroH2A1.2 at fragile regions, whereas macroH2A1.2 loss in these cells triggers DNA damage signaling-dependent senescence, a hallmark of RS. Altogether, our findings demonstrate that recurrent DNA damage contributes to the chromatin landscape to ensure the epigenomic integrity of dividing cells.

논문정보 - 형식: Research article - 게재일: 2017년 12월 (BRIC 등록일 2017-12-20) - 연구진: 국외연구진 - 분야: Molecular_BiologyCell_BiologyGenomics

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