期刊
MOLECULAR THERAPY
卷 26, 期 4, 页码 1154-1165出版社
CELL PRESS
DOI: 10.1016/j.ymthe.2018.02.003
关键词
-
资金
- National Research Foundation of Korea - Ministry of Science, ICT & Future Planning [2017R1A2B2005603]
- Next-Generation BioGreen 21 Program (SSAC) [PJ01322801]
- Rural Development Administration, Republic of Korea
- National Research Foundation of Korea [2017R1A2B2005603] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Homologous recombination (HR), which ensures accurate DNA replication and strand-break repair, is necessary to preserve embryonic stem cell (ESC) self-renewal. However, little is known about how HR factors modulate ESC differentiation and replication stress-associated DNA breaks caused by unique cell-cycle progression. Here, we report that ESCs utilize Rad51-dependent HR to enhance viability and induce rapid proliferation through a replication-coupled pathway. In addition, ESC differentiation was shown to be enhanced by ectopic expression of a subset of recombinases. Abundant expression of HR proteins throughout the ESC cycle, but not during differentiation, facilitated immediate HR-mediated repair of single-stranded DNA (ssDNA) gaps incurred during S-phase, via amechanism that does not perturb cellular progression. Intriguingly, combined ectopic expression of two recombinases, Rad51 and Rad52, resulted in efficient ESC differentiation and diminished cell death, indicating that HR factors promote cellular differentiation by repairing global DNA breaks induced by chromatin remodeling signals. Collectively, these findings provide insight into the role of key HR factors in rapid DNA break repair following chromosome duplication during self-renewal and differentiation of ESCs.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据