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Role for hACF1 in the G2/M damage checkpoint

Active chromatin remodelling is integral to the DNA damage response in eukaryotes, as damage sensors, signalling molecules and repair enzymes gain access to lesions. A variety of nucleosome remodelling complexes is known to promote different stages of DNA repair. The nucleosome sliding factors CHRAC...

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Autores principales: Sánchez-Molina, Sara, Mortusewicz, Oliver, Bieber, Béatrice, Auer, Susanne, Eckey, Maren, Leonhardt, Heinrich, Friedl, Anna A., Becker, Peter B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3201854/
https://www.ncbi.nlm.nih.gov/pubmed/21745822
http://dx.doi.org/10.1093/nar/gkr435
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author Sánchez-Molina, Sara
Mortusewicz, Oliver
Bieber, Béatrice
Auer, Susanne
Eckey, Maren
Leonhardt, Heinrich
Friedl, Anna A.
Becker, Peter B.
author_facet Sánchez-Molina, Sara
Mortusewicz, Oliver
Bieber, Béatrice
Auer, Susanne
Eckey, Maren
Leonhardt, Heinrich
Friedl, Anna A.
Becker, Peter B.
author_sort Sánchez-Molina, Sara
collection PubMed
description Active chromatin remodelling is integral to the DNA damage response in eukaryotes, as damage sensors, signalling molecules and repair enzymes gain access to lesions. A variety of nucleosome remodelling complexes is known to promote different stages of DNA repair. The nucleosome sliding factors CHRAC/ACF of Drosophila are involved in chromatin organization during development. Involvement of corresponding hACF1-containing mammalian nucleosome sliding factors in replication, transcription and very recently also non-homologous end-joining of DNA breaks have been suggested. We now found that hACF1-containing factors are more generally involved in the DNA damage response. hACF1 depletion increases apoptosis, sensitivity to radiation and compromises the G2/M arrest that is activated in response to UV- and X-rays. In the absence of hACF1, γH2AX and CHK2ph signals are diminished. hACF1 and its ATPase partner SNF2H rapidly accumulate at sites of laser-induced DNA damage. hACF1 is also required for a tight checkpoint that is induced upon replication fork collapse. ACF1-depleted cells that are challenged with aphidicolin enter mitosis despite persistence of lesions and accumulate breaks in metaphase chromosomes. hACF1-containing remodellers emerge as global facilitators of the cellular response to a variety of different types of DNA damage.
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spelling pubmed-32018542011-10-26 Role for hACF1 in the G2/M damage checkpoint Sánchez-Molina, Sara Mortusewicz, Oliver Bieber, Béatrice Auer, Susanne Eckey, Maren Leonhardt, Heinrich Friedl, Anna A. Becker, Peter B. Nucleic Acids Res Genome Integrity, Repair and Replication Active chromatin remodelling is integral to the DNA damage response in eukaryotes, as damage sensors, signalling molecules and repair enzymes gain access to lesions. A variety of nucleosome remodelling complexes is known to promote different stages of DNA repair. The nucleosome sliding factors CHRAC/ACF of Drosophila are involved in chromatin organization during development. Involvement of corresponding hACF1-containing mammalian nucleosome sliding factors in replication, transcription and very recently also non-homologous end-joining of DNA breaks have been suggested. We now found that hACF1-containing factors are more generally involved in the DNA damage response. hACF1 depletion increases apoptosis, sensitivity to radiation and compromises the G2/M arrest that is activated in response to UV- and X-rays. In the absence of hACF1, γH2AX and CHK2ph signals are diminished. hACF1 and its ATPase partner SNF2H rapidly accumulate at sites of laser-induced DNA damage. hACF1 is also required for a tight checkpoint that is induced upon replication fork collapse. ACF1-depleted cells that are challenged with aphidicolin enter mitosis despite persistence of lesions and accumulate breaks in metaphase chromosomes. hACF1-containing remodellers emerge as global facilitators of the cellular response to a variety of different types of DNA damage. Oxford University Press 2011-10 2011-07-11 /pmc/articles/PMC3201854/ /pubmed/21745822 http://dx.doi.org/10.1093/nar/gkr435 Text en © The Author(s) 2011. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Genome Integrity, Repair and Replication
Sánchez-Molina, Sara
Mortusewicz, Oliver
Bieber, Béatrice
Auer, Susanne
Eckey, Maren
Leonhardt, Heinrich
Friedl, Anna A.
Becker, Peter B.
Role for hACF1 in the G2/M damage checkpoint
title Role for hACF1 in the G2/M damage checkpoint
title_full Role for hACF1 in the G2/M damage checkpoint
title_fullStr Role for hACF1 in the G2/M damage checkpoint
title_full_unstemmed Role for hACF1 in the G2/M damage checkpoint
title_short Role for hACF1 in the G2/M damage checkpoint
title_sort role for hacf1 in the g2/m damage checkpoint
topic Genome Integrity, Repair and Replication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3201854/
https://www.ncbi.nlm.nih.gov/pubmed/21745822
http://dx.doi.org/10.1093/nar/gkr435
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