Affiliation:
1. Departamento de Genética, Facultad de Biología Universidad de Sevilla Sevilla Spain
2. Centro Andaluz de Biología Molecular y Medicina Regenerativa‐CABIMER Universidad de Sevilla‐CSIC‐Universidad Pablo de Olavide Sevilla Spain
3. Genome Data Science, Institute for Research in Biomedicine (IRB Barcelona) The Barcelona Institute of Science and Technology (BIST) Barcelona Spain
4. Department of Cell Biology, Sciences III University of Geneva Geneva Switzerland
Abstract
AbstractThe centrosome is a cytoplasmic organelle with roles in microtubule organization that has also been proposed to act as a hub for cellular signaling. Some centrosomal components are required for full activation of the DNA damage response. However, whether the centrosome regulates specific DNA repair pathways is not known. Here, we show that centrosome presence is required to fully activate recombination, specifically to completely license its initial step, the so‐called DNA end resection. Furthermore, we identify a centriolar structure, the subdistal appendages, and a specific factor, CEP170, as the critical centrosomal component involved in the regulation of recombination and resection. Cells lacking centrosomes or depleted for CEP170 are, consequently, hypersensitive to DNA damaging agents. Moreover, low levels of CEP170 in multiple cancer types correlate with an increase of the mutation burden associated with specific mutational signatures and a better prognosis, suggesting that changes in CEP170 can act as a mutation driver but could also be targeted to improve current oncological treatments.
Funder
European Molecular Biology Organization
Universidad de Sevilla
Publisher
Springer Science and Business Media LLC
Subject
Genetics,Molecular Biology,Biochemistry
Cited by
3 articles.
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