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A role of the 53BP1 protein in genome protection: structural and functional characteristics of 53BP1-dependent DNA repair
Nuclear architecture plays a significant role in DNA repair mechanisms. It is evident that proteins involved in DNA repair are compartmentalized in not only spontaneously occurring DNA lesions or ionizing radiation-induced foci (IRIF), but a specific clustering of these proteins can also be observed...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6519998/ https://www.ncbi.nlm.nih.gov/pubmed/30996128 http://dx.doi.org/10.18632/aging.101917 |
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author | Bártová, Eva Legartová, Soňa Dundr, Miroslav Suchánková, Jana |
author_facet | Bártová, Eva Legartová, Soňa Dundr, Miroslav Suchánková, Jana |
author_sort | Bártová, Eva |
collection | PubMed |
description | Nuclear architecture plays a significant role in DNA repair mechanisms. It is evident that proteins involved in DNA repair are compartmentalized in not only spontaneously occurring DNA lesions or ionizing radiation-induced foci (IRIF), but a specific clustering of these proteins can also be observed within the whole cell nucleus. For example, 53BP1-positive and BRCA1-positive DNA repair foci decorate chromocenters and can appear close to nuclear speckles. Both 53BP1 and BRCA1 are well-described factors that play an essential role in double-strand break (DSB) repair. These proteins are members of two protein complexes: 53BP1-RIF1-PTIP and BRCA1-CtIP, which make a “decision” determining whether canonical nonhomologous end joining (NHEJ) or homology-directed repair (HDR) is activated. It is generally accepted that 53BP1 mediates the NHEJ mechanism, while HDR is activated via a BRCA1-dependent signaling pathway. Interestingly, the 53BP1 protein appears relatively quickly at DSB sites, while BRCA1 is functional at later stages of DNA repair, as soon as the Mre11-Rad50-Nbs1 complex is recruited to the DNA lesions. A function of the 53BP1 protein is also linked to a specific histone signature, including phosphorylation of histone H2AX (γH2AX) or methylation of histone H4 at the lysine 20 position (H4K20me); therefore, we also discuss an epigenetic landscape of 53BP1-positive DNA lesions. |
format | Online Article Text |
id | pubmed-6519998 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Impact Journals |
record_format | MEDLINE/PubMed |
spelling | pubmed-65199982019-05-29 A role of the 53BP1 protein in genome protection: structural and functional characteristics of 53BP1-dependent DNA repair Bártová, Eva Legartová, Soňa Dundr, Miroslav Suchánková, Jana Aging (Albany NY) Review Nuclear architecture plays a significant role in DNA repair mechanisms. It is evident that proteins involved in DNA repair are compartmentalized in not only spontaneously occurring DNA lesions or ionizing radiation-induced foci (IRIF), but a specific clustering of these proteins can also be observed within the whole cell nucleus. For example, 53BP1-positive and BRCA1-positive DNA repair foci decorate chromocenters and can appear close to nuclear speckles. Both 53BP1 and BRCA1 are well-described factors that play an essential role in double-strand break (DSB) repair. These proteins are members of two protein complexes: 53BP1-RIF1-PTIP and BRCA1-CtIP, which make a “decision” determining whether canonical nonhomologous end joining (NHEJ) or homology-directed repair (HDR) is activated. It is generally accepted that 53BP1 mediates the NHEJ mechanism, while HDR is activated via a BRCA1-dependent signaling pathway. Interestingly, the 53BP1 protein appears relatively quickly at DSB sites, while BRCA1 is functional at later stages of DNA repair, as soon as the Mre11-Rad50-Nbs1 complex is recruited to the DNA lesions. A function of the 53BP1 protein is also linked to a specific histone signature, including phosphorylation of histone H2AX (γH2AX) or methylation of histone H4 at the lysine 20 position (H4K20me); therefore, we also discuss an epigenetic landscape of 53BP1-positive DNA lesions. Impact Journals 2019-04-17 /pmc/articles/PMC6519998/ /pubmed/30996128 http://dx.doi.org/10.18632/aging.101917 Text en Copyright © 2019 Bártová et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY) 3.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Review Bártová, Eva Legartová, Soňa Dundr, Miroslav Suchánková, Jana A role of the 53BP1 protein in genome protection: structural and functional characteristics of 53BP1-dependent DNA repair |
title | A role of the 53BP1 protein in genome protection: structural and functional characteristics of 53BP1-dependent DNA repair |
title_full | A role of the 53BP1 protein in genome protection: structural and functional characteristics of 53BP1-dependent DNA repair |
title_fullStr | A role of the 53BP1 protein in genome protection: structural and functional characteristics of 53BP1-dependent DNA repair |
title_full_unstemmed | A role of the 53BP1 protein in genome protection: structural and functional characteristics of 53BP1-dependent DNA repair |
title_short | A role of the 53BP1 protein in genome protection: structural and functional characteristics of 53BP1-dependent DNA repair |
title_sort | role of the 53bp1 protein in genome protection: structural and functional characteristics of 53bp1-dependent dna repair |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6519998/ https://www.ncbi.nlm.nih.gov/pubmed/30996128 http://dx.doi.org/10.18632/aging.101917 |
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