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Combined Ectopic Expression of Homologous Recombination Factors Promotes Embryonic Stem Cell Differentiation
| Content Provider | Scilit |
|---|---|
| Author | Choi, Eui-Hwan Yoon, Seobin Kim, Keun P. |
| Copyright Year | 2018 |
| Description | Journal: Molecular Therapy Homologous recombination (HR), which ensures accurate DNA replication and strand-break repair, is necessary to preserve embryonic stem (ES) cell self-renewal. However, little is known about how HR factors modulate ES cell differentiation and replication stress-associated DNA breaks caused by unique cell cycle progression. Here, we report that ES cells utilize Rad51-dependent HR to enhance viability and induce rapid proliferation through a replication-coupled pathway. In addition, ES cell differentiation was shown to be enhanced by ectopic expression of a subset of recombinases. Abundant expression of HR proteins throughout the ES cell cycle, but not during differentiation, facilitated immediate HR-mediated repair of single-stranded DNA (ssDNA) gaps incurred during S-phase, via a mechanism that does not perturb cellular progression. Intriguingly, combined ectopic expression of two recombinases—Rad51 and Rad52—resulted in efficient ES cell 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 ES cells. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6079475/pdf http://www.cell.com/article/S152500161830056X/pdf |
| Ending Page | 1165 |
| Page Count | 12 |
| Starting Page | 1154 |
| ISSN | 15250016 |
| e-ISSN | 15250024 |
| DOI | 10.1016/j.ymthe.2018.02.003 |
| Journal | Molecular Therapy |
| Issue Number | 4 |
| Volume Number | 26 |
| Language | English |
| Publisher | Elsevier BV |
| Publisher Date | 2018-02-07 |
| Access Restriction | Open |
| Subject Keyword | Journal: Molecular Therapy Cell Tissue Engineering Embryonic Stem Cells Cell Differentiation Homologous Recombination |
| Content Type | Text |
| Resource Type | Article |
| Subject | Genetics Medicine Drug Discovery Molecular Biology Molecular Medicine Pharmacology |
