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MRN, CtIP, and BRCA1 mediate repair of topoisomerase II–DNA adducts
Repair of DNA double-strand breaks (DSBs) with complex ends poses a special challenge, as additional processing is required before DNA ligation. For example, protein–DNA adducts must be removed to allow repair by either nonhomologous end joining or homology-directed repair. Here, we investigated the...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4754713/ https://www.ncbi.nlm.nih.gov/pubmed/26880199 http://dx.doi.org/10.1083/jcb.201504005 |
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author | Aparicio, Tomas Baer, Richard Gottesman, Max Gautier, Jean |
author_facet | Aparicio, Tomas Baer, Richard Gottesman, Max Gautier, Jean |
author_sort | Aparicio, Tomas |
collection | PubMed |
description | Repair of DNA double-strand breaks (DSBs) with complex ends poses a special challenge, as additional processing is required before DNA ligation. For example, protein–DNA adducts must be removed to allow repair by either nonhomologous end joining or homology-directed repair. Here, we investigated the processing of topoisomerase II (Top2)–DNA adducts induced by treatment with the chemotherapeutic agent etoposide. Through biochemical analysis in Xenopus laevis egg extracts, we establish that the MRN (Mre11, Rad50, and Nbs1) complex, CtIP, and BRCA1 are required for both the removal of Top2–DNA adducts and the subsequent resection of Top2-adducted DSB ends. Moreover, the interaction between CtIP and BRCA1, although dispensable for resection of endonuclease-generated DSB ends, is required for resection of Top2-adducted DSBs, as well as for cellular resistance to etoposide during genomic DNA replication. |
format | Online Article Text |
id | pubmed-4754713 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-47547132016-08-15 MRN, CtIP, and BRCA1 mediate repair of topoisomerase II–DNA adducts Aparicio, Tomas Baer, Richard Gottesman, Max Gautier, Jean J Cell Biol Research Articles Repair of DNA double-strand breaks (DSBs) with complex ends poses a special challenge, as additional processing is required before DNA ligation. For example, protein–DNA adducts must be removed to allow repair by either nonhomologous end joining or homology-directed repair. Here, we investigated the processing of topoisomerase II (Top2)–DNA adducts induced by treatment with the chemotherapeutic agent etoposide. Through biochemical analysis in Xenopus laevis egg extracts, we establish that the MRN (Mre11, Rad50, and Nbs1) complex, CtIP, and BRCA1 are required for both the removal of Top2–DNA adducts and the subsequent resection of Top2-adducted DSB ends. Moreover, the interaction between CtIP and BRCA1, although dispensable for resection of endonuclease-generated DSB ends, is required for resection of Top2-adducted DSBs, as well as for cellular resistance to etoposide during genomic DNA replication. The Rockefeller University Press 2016-02-15 /pmc/articles/PMC4754713/ /pubmed/26880199 http://dx.doi.org/10.1083/jcb.201504005 Text en © 2016 Aparicio et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Research Articles Aparicio, Tomas Baer, Richard Gottesman, Max Gautier, Jean MRN, CtIP, and BRCA1 mediate repair of topoisomerase II–DNA adducts |
title | MRN, CtIP, and BRCA1 mediate repair of topoisomerase II–DNA adducts |
title_full | MRN, CtIP, and BRCA1 mediate repair of topoisomerase II–DNA adducts |
title_fullStr | MRN, CtIP, and BRCA1 mediate repair of topoisomerase II–DNA adducts |
title_full_unstemmed | MRN, CtIP, and BRCA1 mediate repair of topoisomerase II–DNA adducts |
title_short | MRN, CtIP, and BRCA1 mediate repair of topoisomerase II–DNA adducts |
title_sort | mrn, ctip, and brca1 mediate repair of topoisomerase ii–dna adducts |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4754713/ https://www.ncbi.nlm.nih.gov/pubmed/26880199 http://dx.doi.org/10.1083/jcb.201504005 |
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