ALC1/eIF4A1-mediated regulation of CtIP mRNA stability controls DNA end resection

Autoři: Fernando Mejías-Navarro aff001;  Guillermo Rodríguez-Real aff001;  Javier Ramón aff001;  Rosa Camarillo aff001;  Pablo Huertas aff001
Působiště autorů: Department of Genetics, University of Seville, Sevilla, Spain aff001;  Centro Andaluz de Biología Molecular y Medicina Regenerativa-CABIMER, Universidad de Sevilla-CSIC-Universidad Pablo de Olavide, Sevilla, Spain aff002
Vyšlo v časopise: ALC1/eIF4A1-mediated regulation of CtIP mRNA stability controls DNA end resection. PLoS Genet 16(5): e32767. doi:10.1371/journal.pgen.1008787
Kategorie: Research Article
doi: 10.1371/journal.pgen.1008787


During repair of DNA double-strand breaks, resection of DNA ends influences how these lesions will be repaired. If resection is activated, the break will be channeled through homologous recombination; if not, it will be simply ligated using the non-homologous end-joining machinery. Regulation of resection relies greatly on modulating CtIP, which can be done by modifying: i) its interaction partners, ii) its post-translational modifications, or iii) its cellular levels, by regulating transcription, splicing and/or protein stability/degradation. Here, we have analyzed the role of ALC1, a chromatin remodeler previously described as an integral part of the DNA damage response, in resection. Strikingly, we found that ALC1 affects resection independently of chromatin remodeling activity or its ability to bind damaged chromatin. In fact, it cooperates with the RNA-helicase eIF4A1 to help stabilize the most abundant splicing form of CtIP mRNA. This function relies on the presence of a specific RNA sequence in the 5′ UTR of CtIP. Therefore, we describe an additional layer of regulation of CtIP—at the level of mRNA stability through ALC1 and eIF4A1.

Klíčová slova:

Cell cycle and cell division – DNA damage – Chromatin – Messenger RNA – Non-homologous end joining – Recombinase polymerase amplification – Small interfering RNAs – Surgical resection


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