A non-transcriptional function of Yap regulates the DNA replication program in Xenopus laevis
| Autor: | Olivier Haccard, Rodrigo Meléndez García, Albert Chesneau, Hemalatha Narassimprakash, Jérôme Roger, Muriel Perron, Kathrin Marheineke, Odile Bronchain |
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| Přispěvatelé: | Institut des Neurosciences Paris-Saclay (NeuroPSI), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
trim-away
General Immunology and Microbiology [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior General Neuroscience Xenopus [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology hippo/yap pathway MESH: S Phase [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences MESH: DNA Replication General Medicine DNA replication General Biochemistry Genetics and Molecular Biology MESH: Telomere-Binding Proteins developmental biology retinal stem cells Rif1 MESH: Xenopus laevis cell biology MESH: Replication Origin MESH: Animals MESH: DNA Replication Timing |
| Zdroj: | eLife eLife, 2022, 11, pp.e75741. ⟨10.7554/eLife.75741⟩ |
| ISSN: | 2050-084X |
| Popis: | In multicellular eukaryotic organisms, the initiation of DNA replication occurs asynchronously throughout S-phase according to a regulated replication timing program. Here, using Xenopus egg extracts, we showed that Yap (Yes-associated protein 1), a downstream effector of the Hippo signalling pathway, is required for the control of DNA replication dynamics. We found that Yap is recruited to chromatin at the start of DNA replication and identified Rif1, a major regulator of the DNA replication timing program, as a novel Yap binding protein. Furthermore, we show that either Yap or Rif1 depletion accelerates DNA replication dynamics by increasing the number of activated replication origins. In Xenopus embryos, using a Trim-Away approach during cleavage stages devoid of transcription, we found that either Yap or Rif1 depletion triggers an acceleration of cell divisions, suggesting a shorter S-phase by alterations of the replication program. Finally, our data show that Rif1 knockdown leads to defects in the partitioning of early versus late replication foci in retinal stem cells, as we previously showed for Yap. Altogether, our findings unveil a non-transcriptional role for Yap in regulating replication dynamics. We propose that Yap and Rif1 function as brakes to control the DNA replication program in early embryos and post-embryonic stem cells. |
| Databáze: | OpenAIRE |
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