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Human single-stranded DNA binding protein 1 (hSSB1/NABP2) is required for the stability and repair of stalled replication forks
Aberrant DNA replication is a primary cause of mutations that are associated with pathological disorders including cancer. During DNA metabolism, the primary causes of replication fork stalling include secondary DNA structures, highly transcribed regions and damaged DNA. The restart of stalled repli...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4041449/ https://www.ncbi.nlm.nih.gov/pubmed/24753408 http://dx.doi.org/10.1093/nar/gku276 |
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author | Bolderson, Emma Petermann, Eva Croft, Laura Suraweera, Amila Pandita, Raj K. Pandita, Tej K. Helleday, Thomas Khanna, Kum Kum Richard, Derek J. |
author_facet | Bolderson, Emma Petermann, Eva Croft, Laura Suraweera, Amila Pandita, Raj K. Pandita, Tej K. Helleday, Thomas Khanna, Kum Kum Richard, Derek J. |
author_sort | Bolderson, Emma |
collection | PubMed |
description | Aberrant DNA replication is a primary cause of mutations that are associated with pathological disorders including cancer. During DNA metabolism, the primary causes of replication fork stalling include secondary DNA structures, highly transcribed regions and damaged DNA. The restart of stalled replication forks is critical for the timely progression of the cell cycle and ultimately for the maintenance of genomic stability. Our previous work has implicated the single-stranded DNA binding protein, hSSB1/NABP2, in the repair of DNA double-strand breaks via homologous recombination. Here, we demonstrate that hSSB1 relocates to hydroxyurea (HU)-damaged replication forks where it is required for ATR and Chk1 activation and recruitment of Mre11 and Rad51. Consequently, hSSB1-depleted cells fail to repair and restart stalled replication forks. hSSB1 deficiency causes accumulation of DNA strand breaks and results in chromosome aberrations observed in mitosis, ultimately resulting in hSSB1 being required for survival to HU and camptothecin. Overall, our findings demonstrate the importance of hSSB1 in maintaining and repairing DNA replication forks and for overall genomic stability. |
format | Online Article Text |
id | pubmed-4041449 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-40414492014-06-11 Human single-stranded DNA binding protein 1 (hSSB1/NABP2) is required for the stability and repair of stalled replication forks Bolderson, Emma Petermann, Eva Croft, Laura Suraweera, Amila Pandita, Raj K. Pandita, Tej K. Helleday, Thomas Khanna, Kum Kum Richard, Derek J. Nucleic Acids Res Genome Integrity, Repair and Replication Aberrant DNA replication is a primary cause of mutations that are associated with pathological disorders including cancer. During DNA metabolism, the primary causes of replication fork stalling include secondary DNA structures, highly transcribed regions and damaged DNA. The restart of stalled replication forks is critical for the timely progression of the cell cycle and ultimately for the maintenance of genomic stability. Our previous work has implicated the single-stranded DNA binding protein, hSSB1/NABP2, in the repair of DNA double-strand breaks via homologous recombination. Here, we demonstrate that hSSB1 relocates to hydroxyurea (HU)-damaged replication forks where it is required for ATR and Chk1 activation and recruitment of Mre11 and Rad51. Consequently, hSSB1-depleted cells fail to repair and restart stalled replication forks. hSSB1 deficiency causes accumulation of DNA strand breaks and results in chromosome aberrations observed in mitosis, ultimately resulting in hSSB1 being required for survival to HU and camptothecin. Overall, our findings demonstrate the importance of hSSB1 in maintaining and repairing DNA replication forks and for overall genomic stability. Oxford University Press 2014-06-01 2014-05-05 /pmc/articles/PMC4041449/ /pubmed/24753408 http://dx.doi.org/10.1093/nar/gku276 Text en © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited |
spellingShingle | Genome Integrity, Repair and Replication Bolderson, Emma Petermann, Eva Croft, Laura Suraweera, Amila Pandita, Raj K. Pandita, Tej K. Helleday, Thomas Khanna, Kum Kum Richard, Derek J. Human single-stranded DNA binding protein 1 (hSSB1/NABP2) is required for the stability and repair of stalled replication forks |
title | Human single-stranded DNA binding protein 1 (hSSB1/NABP2) is required for the stability and repair of stalled replication forks |
title_full | Human single-stranded DNA binding protein 1 (hSSB1/NABP2) is required for the stability and repair of stalled replication forks |
title_fullStr | Human single-stranded DNA binding protein 1 (hSSB1/NABP2) is required for the stability and repair of stalled replication forks |
title_full_unstemmed | Human single-stranded DNA binding protein 1 (hSSB1/NABP2) is required for the stability and repair of stalled replication forks |
title_short | Human single-stranded DNA binding protein 1 (hSSB1/NABP2) is required for the stability and repair of stalled replication forks |
title_sort | human single-stranded dna binding protein 1 (hssb1/nabp2) is required for the stability and repair of stalled replication forks |
topic | Genome Integrity, Repair and Replication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4041449/ https://www.ncbi.nlm.nih.gov/pubmed/24753408 http://dx.doi.org/10.1093/nar/gku276 |
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