YAP controls retinal stem cell DNA replication timing and genomic stability
| Title: | YAP controls retinal stem cell DNA replication timing and genomic stability |
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| Authors: | Pauline Cabochette, Guillermo Vega-Lopez, Juliette Bitard, Karine Parain, Romain Chemouny, Christel Masson, Caroline Borday, Marie Hedderich, Kristine A Henningfeld, Morgane Locker, Odile Bronchain, Muriel Perron |
| Source: | eLife, Vol 4 (2015) |
| Publisher Information: | eLife Sciences Publications Ltd, 2015. |
| Publication Year: | 2015 |
| Collection: | LCC:Medicine LCC:Science LCC:Biology (General) |
| Subject Terms: | retina, neural stem cell, Hippo/Yap pathway, cell proliferation, ciliary marginal zone, Medicine, Science, Biology (General), QH301-705.5 |
| More Details: | The adult frog retina retains a reservoir of active neural stem cells that contribute to continuous eye growth throughout life. We found that Yap, a downstream effector of the Hippo pathway, is specifically expressed in these stem cells. Yap knock-down leads to an accelerated S-phase and an abnormal progression of DNA replication, a phenotype likely mediated by upregulation of c-Myc. This is associated with an increased occurrence of DNA damage and eventually p53-p21 pathway-mediated cell death. Finally, we identified PKNOX1, a transcription factor involved in the maintenance of genomic stability, as a functional and physical interactant of YAP. Altogether, we propose that YAP is required in adult retinal stem cells to regulate the temporal firing of replication origins and quality control of replicated DNA. Our data reinforce the view that specific mechanisms dedicated to S-phase control are at work in stem cells to protect them from genomic instability. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 2050-084X |
| Relation: | https://elifesciences.org/articles/08488; https://doaj.org/toc/2050-084X |
| DOI: | 10.7554/eLife.08488 |
| Access URL: | https://doaj.org/article/d8299e71dae248db9470842400591f76 |
| Accession Number: | edsdoj.8299e71dae248db9470842400591f76 |
| Database: | Directory of Open Access Journals |
| ISSN: | 2050084X |
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| DOI: | 10.7554/eLife.08488 |
| Published in: | eLife |
| Language: | English |