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The human Shu complex functions with PDS5B and SPIDR to promote homologous recombination
RAD51 plays a central role in homologous recombination during double-strand break repair and in replication fork dynamics. Misregulation of RAD51 is associated with genetic instability and cancer. RAD51 is regulated by many accessory proteins including the highly conserved Shu complex. Here, we repo...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6821187/ https://www.ncbi.nlm.nih.gov/pubmed/31665741 http://dx.doi.org/10.1093/nar/gkz738 |
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author | Martino, Julieta Brunette, Gregory J Barroso-González, Jonathan Moiseeva, Tatiana N Smith, Chelsea M Bakkenist, Christopher J O’Sullivan, Roderick J Bernstein, Kara A |
author_facet | Martino, Julieta Brunette, Gregory J Barroso-González, Jonathan Moiseeva, Tatiana N Smith, Chelsea M Bakkenist, Christopher J O’Sullivan, Roderick J Bernstein, Kara A |
author_sort | Martino, Julieta |
collection | PubMed |
description | RAD51 plays a central role in homologous recombination during double-strand break repair and in replication fork dynamics. Misregulation of RAD51 is associated with genetic instability and cancer. RAD51 is regulated by many accessory proteins including the highly conserved Shu complex. Here, we report the function of the human Shu complex during replication to regulate RAD51 recruitment to DNA repair foci and, secondly, during replication fork restart following replication fork stalling. Deletion of the Shu complex members, SWS1 and SWSAP1, using CRISPR/Cas9, renders cells specifically sensitive to the replication fork stalling and collapse caused by methyl methanesulfonate and mitomycin C exposure, a delayed and reduced RAD51 response, and fewer sister chromatid exchanges. Our additional analysis identified SPIDR and PDS5B as novel Shu complex interacting partners and genetically function in the same pathway upon DNA damage. Collectively, our study uncovers a protein complex, which consists of SWS1, SWSAP1, SPIDR and PDS5B, involved in DNA repair and provides insight into Shu complex function and composition. |
format | Online Article Text |
id | pubmed-6821187 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-68211872019-11-04 The human Shu complex functions with PDS5B and SPIDR to promote homologous recombination Martino, Julieta Brunette, Gregory J Barroso-González, Jonathan Moiseeva, Tatiana N Smith, Chelsea M Bakkenist, Christopher J O’Sullivan, Roderick J Bernstein, Kara A Nucleic Acids Res Genome Integrity, Repair and Replication RAD51 plays a central role in homologous recombination during double-strand break repair and in replication fork dynamics. Misregulation of RAD51 is associated with genetic instability and cancer. RAD51 is regulated by many accessory proteins including the highly conserved Shu complex. Here, we report the function of the human Shu complex during replication to regulate RAD51 recruitment to DNA repair foci and, secondly, during replication fork restart following replication fork stalling. Deletion of the Shu complex members, SWS1 and SWSAP1, using CRISPR/Cas9, renders cells specifically sensitive to the replication fork stalling and collapse caused by methyl methanesulfonate and mitomycin C exposure, a delayed and reduced RAD51 response, and fewer sister chromatid exchanges. Our additional analysis identified SPIDR and PDS5B as novel Shu complex interacting partners and genetically function in the same pathway upon DNA damage. Collectively, our study uncovers a protein complex, which consists of SWS1, SWSAP1, SPIDR and PDS5B, involved in DNA repair and provides insight into Shu complex function and composition. Oxford University Press 2019-11-04 2019-09-06 /pmc/articles/PMC6821187/ /pubmed/31665741 http://dx.doi.org/10.1093/nar/gkz738 Text en © The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Genome Integrity, Repair and Replication Martino, Julieta Brunette, Gregory J Barroso-González, Jonathan Moiseeva, Tatiana N Smith, Chelsea M Bakkenist, Christopher J O’Sullivan, Roderick J Bernstein, Kara A The human Shu complex functions with PDS5B and SPIDR to promote homologous recombination |
title | The human Shu complex functions with PDS5B and SPIDR to promote homologous recombination |
title_full | The human Shu complex functions with PDS5B and SPIDR to promote homologous recombination |
title_fullStr | The human Shu complex functions with PDS5B and SPIDR to promote homologous recombination |
title_full_unstemmed | The human Shu complex functions with PDS5B and SPIDR to promote homologous recombination |
title_short | The human Shu complex functions with PDS5B and SPIDR to promote homologous recombination |
title_sort | human shu complex functions with pds5b and spidr to promote homologous recombination |
topic | Genome Integrity, Repair and Replication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6821187/ https://www.ncbi.nlm.nih.gov/pubmed/31665741 http://dx.doi.org/10.1093/nar/gkz738 |
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