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TOPBP1(Dpb11) plays a conserved role in homologous recombination DNA repair through the coordinated recruitment of 53BP1(Rad9)
Genome maintenance and cancer suppression require homologous recombination (HR) DNA repair. In yeast and mammals, the scaffold protein TOPBP1(Dpb11) has been implicated in HR, although its precise function and mechanism of action remain elusive. In this study, we show that yeast Dpb11 plays an antag...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5350513/ https://www.ncbi.nlm.nih.gov/pubmed/28228534 http://dx.doi.org/10.1083/jcb.201607031 |
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author | Liu, Yi Cussiol, José Renato Dibitetto, Diego Sims, Jennie Rae Twayana, Shyam Weiss, Robert Samuel Freire, Raimundo Marini, Federica Pellicioli, Achille Smolka, Marcus Bustamante |
author_facet | Liu, Yi Cussiol, José Renato Dibitetto, Diego Sims, Jennie Rae Twayana, Shyam Weiss, Robert Samuel Freire, Raimundo Marini, Federica Pellicioli, Achille Smolka, Marcus Bustamante |
author_sort | Liu, Yi |
collection | PubMed |
description | Genome maintenance and cancer suppression require homologous recombination (HR) DNA repair. In yeast and mammals, the scaffold protein TOPBP1(Dpb11) has been implicated in HR, although its precise function and mechanism of action remain elusive. In this study, we show that yeast Dpb11 plays an antagonistic role in recombination control through regulated protein interactions. Dpb11 mediates opposing roles in DNA end resection by coordinating both the stabilization and exclusion of Rad9 from DNA lesions. The Mec1 kinase promotes the pro-resection function of Dpb11 by mediating its interaction with the Slx4 scaffold. Human TOPBP1(Dpb11) engages in interactions with the anti-resection factor 53BP1 and the pro-resection factor BRCA1, suggesting that TOPBP1 also mediates opposing functions in HR control. Hyperstabilization of the 53BP1–TOPBP1 interaction enhances the recruitment of 53BP1 to nuclear foci in the S phase, resulting in impaired HR and the accumulation of chromosomal aberrations. Our results support a model in which TOPBP1(Dpb11) plays a conserved role in mediating a phosphoregulated circuitry for the control of recombinational DNA repair. |
format | Online Article Text |
id | pubmed-5350513 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-53505132017-09-06 TOPBP1(Dpb11) plays a conserved role in homologous recombination DNA repair through the coordinated recruitment of 53BP1(Rad9) Liu, Yi Cussiol, José Renato Dibitetto, Diego Sims, Jennie Rae Twayana, Shyam Weiss, Robert Samuel Freire, Raimundo Marini, Federica Pellicioli, Achille Smolka, Marcus Bustamante J Cell Biol Research Articles Genome maintenance and cancer suppression require homologous recombination (HR) DNA repair. In yeast and mammals, the scaffold protein TOPBP1(Dpb11) has been implicated in HR, although its precise function and mechanism of action remain elusive. In this study, we show that yeast Dpb11 plays an antagonistic role in recombination control through regulated protein interactions. Dpb11 mediates opposing roles in DNA end resection by coordinating both the stabilization and exclusion of Rad9 from DNA lesions. The Mec1 kinase promotes the pro-resection function of Dpb11 by mediating its interaction with the Slx4 scaffold. Human TOPBP1(Dpb11) engages in interactions with the anti-resection factor 53BP1 and the pro-resection factor BRCA1, suggesting that TOPBP1 also mediates opposing functions in HR control. Hyperstabilization of the 53BP1–TOPBP1 interaction enhances the recruitment of 53BP1 to nuclear foci in the S phase, resulting in impaired HR and the accumulation of chromosomal aberrations. Our results support a model in which TOPBP1(Dpb11) plays a conserved role in mediating a phosphoregulated circuitry for the control of recombinational DNA repair. The Rockefeller University Press 2017-03-06 /pmc/articles/PMC5350513/ /pubmed/28228534 http://dx.doi.org/10.1083/jcb.201607031 Text en © 2017 Liu et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/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 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Research Articles Liu, Yi Cussiol, José Renato Dibitetto, Diego Sims, Jennie Rae Twayana, Shyam Weiss, Robert Samuel Freire, Raimundo Marini, Federica Pellicioli, Achille Smolka, Marcus Bustamante TOPBP1(Dpb11) plays a conserved role in homologous recombination DNA repair through the coordinated recruitment of 53BP1(Rad9) |
title | TOPBP1(Dpb11) plays a conserved role in homologous recombination DNA repair through the coordinated recruitment of 53BP1(Rad9) |
title_full | TOPBP1(Dpb11) plays a conserved role in homologous recombination DNA repair through the coordinated recruitment of 53BP1(Rad9) |
title_fullStr | TOPBP1(Dpb11) plays a conserved role in homologous recombination DNA repair through the coordinated recruitment of 53BP1(Rad9) |
title_full_unstemmed | TOPBP1(Dpb11) plays a conserved role in homologous recombination DNA repair through the coordinated recruitment of 53BP1(Rad9) |
title_short | TOPBP1(Dpb11) plays a conserved role in homologous recombination DNA repair through the coordinated recruitment of 53BP1(Rad9) |
title_sort | topbp1(dpb11) plays a conserved role in homologous recombination dna repair through the coordinated recruitment of 53bp1(rad9) |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5350513/ https://www.ncbi.nlm.nih.gov/pubmed/28228534 http://dx.doi.org/10.1083/jcb.201607031 |
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