Rodriguez Real, GuillermoDomínguez Calvo, AndrésPrados Carvajal, RosarioBayona Feliu, AleixGomes Pereira, SoniaRomero Balestra, FernandoHuertas Sánchez, Pablo2023-09-072023-09-072023Rodriguez Real, G., Domínguez Calvo, A., Prados Carvajal, R., Bayona Feliu, A., Gomes Pereira, S., Romero Balestra, F. y Huertas Sánchez, P. (2023). Centriolar Subdistal Appendages Promote Double-strand Break Repair Through Homologous Recombination. EMBO reports, e56724. https://doi.org/10.15252/embr.202256724.1469-221Xhttps://hdl.handle.net/11441/148702The 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.application/pdf18 p.engAttribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/CentrosomesCEP170DNA end resectionHomologous recombinationSubdistal appendagesinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccesshttps://doi.org/10.15252/embr.202256724