Centriolar Subdistal Appendages Promote Double-strand Break Repair Through Homologous Recombination
The centrosome is a cytoplasmic organelle with roles in microtu-bule organization that has also been proposed to act as a hub forcellular signaling. Some centrosomal components are required forfull activation of the DNA damage response. However, whether thecentrosome regulates specific DNA repair pa...
| Autores: | , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2023 |
| País: | España |
| Institución: | Universidad de Sevilla (US) |
| Repositorio: | idUS. Depósito de Investigación de la Universidad de Sevilla |
| OAI Identifier: | oai:idus.us.es:11441/148702 |
| Acceso en línea: | https://hdl.handle.net/11441/148702 https://doi.org/10.15252/embr.202256724 |
| Access Level: | acceso abierto |
| Palabra clave: | Centrosomes CEP170 DNA end resection Homologous recombination Subdistal appendages |
| Sumario: | The centrosome is a cytoplasmic organelle with roles in microtu-bule organization that has also been proposed to act as a hub forcellular signaling. Some centrosomal components are required forfull activation of the DNA damage response. However, whether thecentrosome regulates specific DNA repair pathways is not known.Here, we show that centrosome presence is required to fully acti-vate recombination, specifically to completely license its initialstep, the so-called DNA end resection. Furthermore, we identify acentriolar structure, the subdistal appendages, and a specific fac-tor, CEP170, as the critical centrosomal component involved in theregulation of recombination and resection. Cells lacking centro-somes or depleted for CEP170are, consequently, hypersensitive toDNA damaging agents. Moreover, low levels of CEP170in multiplecancer types correlate with an increase of the mutation burdenassociated with specific mutational signatures and a better prog-nosis, suggesting that changes in CEP170can act as a mutationdriver but could also be targeted to improve current oncologicaltreatments. |
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