ALC1/eIF4A1-mediated regulation of CtIP mRNA stability controls DNA end resection.
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 res...
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Online Access: | https://doi.org/10.1371/journal.pgen.1008787 |
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doaj-fd2e6cc2be4e4c9eb9103b14ceebef182021-04-21T13:52:43ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042020-05-01165e100878710.1371/journal.pgen.1008787ALC1/eIF4A1-mediated regulation of CtIP mRNA stability controls DNA end resection.Fernando Mejías-NavarroGuillermo Rodríguez-RealJavier RamónRosa CamarilloPablo HuertasDuring 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.https://doi.org/10.1371/journal.pgen.1008787 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Fernando Mejías-Navarro Guillermo Rodríguez-Real Javier Ramón Rosa Camarillo Pablo Huertas |
spellingShingle |
Fernando Mejías-Navarro Guillermo Rodríguez-Real Javier Ramón Rosa Camarillo Pablo Huertas ALC1/eIF4A1-mediated regulation of CtIP mRNA stability controls DNA end resection. PLoS Genetics |
author_facet |
Fernando Mejías-Navarro Guillermo Rodríguez-Real Javier Ramón Rosa Camarillo Pablo Huertas |
author_sort |
Fernando Mejías-Navarro |
title |
ALC1/eIF4A1-mediated regulation of CtIP mRNA stability controls DNA end resection. |
title_short |
ALC1/eIF4A1-mediated regulation of CtIP mRNA stability controls DNA end resection. |
title_full |
ALC1/eIF4A1-mediated regulation of CtIP mRNA stability controls DNA end resection. |
title_fullStr |
ALC1/eIF4A1-mediated regulation of CtIP mRNA stability controls DNA end resection. |
title_full_unstemmed |
ALC1/eIF4A1-mediated regulation of CtIP mRNA stability controls DNA end resection. |
title_sort |
alc1/eif4a1-mediated regulation of ctip mrna stability controls dna end resection. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Genetics |
issn |
1553-7390 1553-7404 |
publishDate |
2020-05-01 |
description |
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. |
url |
https://doi.org/10.1371/journal.pgen.1008787 |
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