Combined Ectopic Expression of Homologous Recombination Factors Promotes Embryonic Stem Cell Differentiationopen access
- Authors
- Choi, Eui-Hwan; Yoon, Seobin; Kim, Keun Pil
- Issue Date
- Apr-2018
- Publisher
- CELL PRESS
- Keywords
- cell differentiation; embryonic stem cells; homologous recombination; self-renewal
- Citation
- MOLECULAR THERAPY, v.26, no.4, pp 1154 - 1165
- Pages
- 12
- Journal Title
- MOLECULAR THERAPY
- Volume
- 26
- Number
- 4
- Start Page
- 1154
- End Page
- 1165
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/2279
- DOI
- 10.1016/j.ymthe.2018.02.003
- ISSN
- 1525-0016
1525-0024
- Abstract
- 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.
- Files in This Item
-
- Appears in
Collections - College of Natural Sciences > Department of Life Science > 1. Journal Articles
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.