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ATMIN is required for the ATM-mediated signaling and recruitment of 53BP1 to DNA damage sites upon replication stress
Unresolved replication intermediates can block the progression of replication forks and become converted into DNA lesions, hence exacerbating genomic instability. The p53-binding protein 1 (53BP1) forms nuclear bodies at sites of unrepaired DNA lesions to shield these regions against erosion, in a m...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4251980/ https://www.ncbi.nlm.nih.gov/pubmed/25262557 http://dx.doi.org/10.1016/j.dnarep.2014.09.001 |
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author | Schmidt, Luisa Wiedner, Marc Velimezi, Georgia Prochazkova, Jana Owusu, Michel Bauer, Sabine Loizou, Joanna I. |
author_facet | Schmidt, Luisa Wiedner, Marc Velimezi, Georgia Prochazkova, Jana Owusu, Michel Bauer, Sabine Loizou, Joanna I. |
author_sort | Schmidt, Luisa |
collection | PubMed |
description | Unresolved replication intermediates can block the progression of replication forks and become converted into DNA lesions, hence exacerbating genomic instability. The p53-binding protein 1 (53BP1) forms nuclear bodies at sites of unrepaired DNA lesions to shield these regions against erosion, in a manner dependent on the DNA damage kinase ATM. The molecular mechanism by which ATM is activated upon replicative stress to localize the 53BP1 protection complex is unknown. Here we show that the ATM-INteracting protein ATMIN (also known as ASCIZ) is partially required for 53BP1 localization upon replicative stress. Additionally, we demonstrate that ATM activation is impaired in cells lacking ATMIN and we define that ATMIN is required for initiating ATM signaling following replicative stress. Furthermore, loss of ATMIN leads to chromosomal segregation defects. Together these data reveal that chromatin integrity depends on ATMIN upon exposure to replication-induced stress. |
format | Online Article Text |
id | pubmed-4251980 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-42519802014-12-03 ATMIN is required for the ATM-mediated signaling and recruitment of 53BP1 to DNA damage sites upon replication stress Schmidt, Luisa Wiedner, Marc Velimezi, Georgia Prochazkova, Jana Owusu, Michel Bauer, Sabine Loizou, Joanna I. DNA Repair (Amst) Article Unresolved replication intermediates can block the progression of replication forks and become converted into DNA lesions, hence exacerbating genomic instability. The p53-binding protein 1 (53BP1) forms nuclear bodies at sites of unrepaired DNA lesions to shield these regions against erosion, in a manner dependent on the DNA damage kinase ATM. The molecular mechanism by which ATM is activated upon replicative stress to localize the 53BP1 protection complex is unknown. Here we show that the ATM-INteracting protein ATMIN (also known as ASCIZ) is partially required for 53BP1 localization upon replicative stress. Additionally, we demonstrate that ATM activation is impaired in cells lacking ATMIN and we define that ATMIN is required for initiating ATM signaling following replicative stress. Furthermore, loss of ATMIN leads to chromosomal segregation defects. Together these data reveal that chromatin integrity depends on ATMIN upon exposure to replication-induced stress. Elsevier 2014-12 /pmc/articles/PMC4251980/ /pubmed/25262557 http://dx.doi.org/10.1016/j.dnarep.2014.09.001 Text en © 2014 The Authors https://creativecommons.org/licenses/by/3.0/This work is licensed under a Creative Commons Attribution 3.0 Unported License (https://creativecommons.org/licenses/by/3.0/) . |
spellingShingle | Article Schmidt, Luisa Wiedner, Marc Velimezi, Georgia Prochazkova, Jana Owusu, Michel Bauer, Sabine Loizou, Joanna I. ATMIN is required for the ATM-mediated signaling and recruitment of 53BP1 to DNA damage sites upon replication stress |
title | ATMIN is required for the ATM-mediated signaling and recruitment of 53BP1 to DNA damage sites upon replication stress |
title_full | ATMIN is required for the ATM-mediated signaling and recruitment of 53BP1 to DNA damage sites upon replication stress |
title_fullStr | ATMIN is required for the ATM-mediated signaling and recruitment of 53BP1 to DNA damage sites upon replication stress |
title_full_unstemmed | ATMIN is required for the ATM-mediated signaling and recruitment of 53BP1 to DNA damage sites upon replication stress |
title_short | ATMIN is required for the ATM-mediated signaling and recruitment of 53BP1 to DNA damage sites upon replication stress |
title_sort | atmin is required for the atm-mediated signaling and recruitment of 53bp1 to dna damage sites upon replication stress |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4251980/ https://www.ncbi.nlm.nih.gov/pubmed/25262557 http://dx.doi.org/10.1016/j.dnarep.2014.09.001 |
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