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Elife 2015 Sep 22;4:e08488. doi: 10.7554/eLife.08488.
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YAP controls retinal stem cell DNA replication timing and genomic stability.

Cabochette P , Vega-Lopez G , Bitard J , Parain K , Chemouny R , Masson C , Borday C , Hedderich M , Henningfeld KA , Locker M , Bronchain O , Perron M .

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.

PubMed ID: 26393999
PMC ID: PMC4578106
Article link: Elife

Species referenced: Xenopus
Genes referenced: atoh7 cdkn1a fxyd1 h2ax h2ax h3-3a hes4 myc nsg1 pcna pknox1 tafazzin tead1 tead4 tgm2 tp53 wwtr1 yap1
Antibodies: H2afx Ab1 H3f3a Ab12 Pcna Ab1 Yap1 Ab2 Yap1 Ab5
Morpholinos: pknox1 MO1 yap1 MO6 yap1 MO7

Article Images: [+] show captions
References [+] :
Aladjem, Replication in context: dynamic regulation of DNA replication patterns in metazoans. 2007, Pubmed