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PHF6 promotes non‐homologous end joining and G2 checkpoint recovery
The cellular response to DNA breaks is influenced by chromatin compaction. To identify chromatin regulators involved in the DNA damage response, we screened for genes that affect recovery following DNA damage using an RNAi library of chromatin regulators. We identified genes involved in chromatin re...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6944915/ https://www.ncbi.nlm.nih.gov/pubmed/31782600 http://dx.doi.org/10.15252/embr.201948460 |
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author | Warmerdam, Daniël O Alonso‐de Vega, Ignacio Wiegant, Wouter W van den Broek, Bram Rother, Magdalena B Wolthuis, Rob MF Freire, Raimundo van Attikum, Haico Medema, René H Smits, Veronique AJ |
author_facet | Warmerdam, Daniël O Alonso‐de Vega, Ignacio Wiegant, Wouter W van den Broek, Bram Rother, Magdalena B Wolthuis, Rob MF Freire, Raimundo van Attikum, Haico Medema, René H Smits, Veronique AJ |
author_sort | Warmerdam, Daniël O |
collection | PubMed |
description | The cellular response to DNA breaks is influenced by chromatin compaction. To identify chromatin regulators involved in the DNA damage response, we screened for genes that affect recovery following DNA damage using an RNAi library of chromatin regulators. We identified genes involved in chromatin remodeling, sister chromatid cohesion, and histone acetylation not previously associated with checkpoint recovery. Among these is the PHD finger protein 6 (PHF6), a gene mutated in Börjeson–Forssman–Lehmann syndrome and leukemic cancers. We find that loss of PHF6 dramatically compromises checkpoint recovery in G2 phase cells. Moreover, PHF6 is rapidly recruited to sites of DNA lesions in a PARP‐dependent manner and required for efficient DNA repair through classical non‐homologous end joining. These results indicate that PHF6 is a novel DNA damage response regulator that promotes end joining‐mediated repair, thereby stimulating timely recovery from the G2 checkpoint. |
format | Online Article Text |
id | pubmed-6944915 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-69449152020-01-07 PHF6 promotes non‐homologous end joining and G2 checkpoint recovery Warmerdam, Daniël O Alonso‐de Vega, Ignacio Wiegant, Wouter W van den Broek, Bram Rother, Magdalena B Wolthuis, Rob MF Freire, Raimundo van Attikum, Haico Medema, René H Smits, Veronique AJ EMBO Rep Reports The cellular response to DNA breaks is influenced by chromatin compaction. To identify chromatin regulators involved in the DNA damage response, we screened for genes that affect recovery following DNA damage using an RNAi library of chromatin regulators. We identified genes involved in chromatin remodeling, sister chromatid cohesion, and histone acetylation not previously associated with checkpoint recovery. Among these is the PHD finger protein 6 (PHF6), a gene mutated in Börjeson–Forssman–Lehmann syndrome and leukemic cancers. We find that loss of PHF6 dramatically compromises checkpoint recovery in G2 phase cells. Moreover, PHF6 is rapidly recruited to sites of DNA lesions in a PARP‐dependent manner and required for efficient DNA repair through classical non‐homologous end joining. These results indicate that PHF6 is a novel DNA damage response regulator that promotes end joining‐mediated repair, thereby stimulating timely recovery from the G2 checkpoint. John Wiley and Sons Inc. 2019-11-29 2020-01-07 /pmc/articles/PMC6944915/ /pubmed/31782600 http://dx.doi.org/10.15252/embr.201948460 Text en © 2019 The Authors. Published under the terms of the CC BY 4.0 license This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Reports Warmerdam, Daniël O Alonso‐de Vega, Ignacio Wiegant, Wouter W van den Broek, Bram Rother, Magdalena B Wolthuis, Rob MF Freire, Raimundo van Attikum, Haico Medema, René H Smits, Veronique AJ PHF6 promotes non‐homologous end joining and G2 checkpoint recovery |
title | PHF6 promotes non‐homologous end joining and G2 checkpoint recovery |
title_full | PHF6 promotes non‐homologous end joining and G2 checkpoint recovery |
title_fullStr | PHF6 promotes non‐homologous end joining and G2 checkpoint recovery |
title_full_unstemmed | PHF6 promotes non‐homologous end joining and G2 checkpoint recovery |
title_short | PHF6 promotes non‐homologous end joining and G2 checkpoint recovery |
title_sort | phf6 promotes non‐homologous end joining and g2 checkpoint recovery |
topic | Reports |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6944915/ https://www.ncbi.nlm.nih.gov/pubmed/31782600 http://dx.doi.org/10.15252/embr.201948460 |
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