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The role of SLX4 and its associated nucleases in DNA interstrand crosslink repair
A key step in the Fanconi anemia pathway of DNA interstrand crosslink (ICL) repair is the ICL unhooking by dual endonucleolytic incisions. SLX4/FANCP is a large scaffold protein that plays a central role in ICL unhooking. It contains multiple domains that interact with many proteins including three...
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/PMC6411836/ https://www.ncbi.nlm.nih.gov/pubmed/30576517 http://dx.doi.org/10.1093/nar/gky1276 |
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author | Hoogenboom, Wouter S Boonen, Rick A C M Knipscheer, Puck |
author_facet | Hoogenboom, Wouter S Boonen, Rick A C M Knipscheer, Puck |
author_sort | Hoogenboom, Wouter S |
collection | PubMed |
description | A key step in the Fanconi anemia pathway of DNA interstrand crosslink (ICL) repair is the ICL unhooking by dual endonucleolytic incisions. SLX4/FANCP is a large scaffold protein that plays a central role in ICL unhooking. It contains multiple domains that interact with many proteins including three different endonucleases and also acts in several other DNA repair pathways. While it is known that its interaction with the endonuclease XPF-ERCC1 is required for its function in ICL repair, which other domains act in this process is unclear. Here, we used Xenopus egg extracts to determine ICL repair specific features of SLX4. We show that the SLX4-interacting endonuclease SLX1 is not required for ICL repair and demonstrate that all essential SLX4 domains are located at the N-terminal half of the protein. The MLR domain is crucial for the recruitment of XPF-ERCC1 but also has an unanticipated function in recruiting SLX4 to the site of damage. Although we find the BTB is not essential for ICL repair in our system, dimerization of SLX4 could be important. Our data provide new insights into the mechanism by which SLX4 acts in ICL repair. |
format | Online Article Text |
id | pubmed-6411836 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-64118362019-03-15 The role of SLX4 and its associated nucleases in DNA interstrand crosslink repair Hoogenboom, Wouter S Boonen, Rick A C M Knipscheer, Puck Nucleic Acids Res Genome Integrity, Repair and Replication A key step in the Fanconi anemia pathway of DNA interstrand crosslink (ICL) repair is the ICL unhooking by dual endonucleolytic incisions. SLX4/FANCP is a large scaffold protein that plays a central role in ICL unhooking. It contains multiple domains that interact with many proteins including three different endonucleases and also acts in several other DNA repair pathways. While it is known that its interaction with the endonuclease XPF-ERCC1 is required for its function in ICL repair, which other domains act in this process is unclear. Here, we used Xenopus egg extracts to determine ICL repair specific features of SLX4. We show that the SLX4-interacting endonuclease SLX1 is not required for ICL repair and demonstrate that all essential SLX4 domains are located at the N-terminal half of the protein. The MLR domain is crucial for the recruitment of XPF-ERCC1 but also has an unanticipated function in recruiting SLX4 to the site of damage. Although we find the BTB is not essential for ICL repair in our system, dimerization of SLX4 could be important. Our data provide new insights into the mechanism by which SLX4 acts in ICL repair. Oxford University Press 2019-03-18 2018-12-21 /pmc/articles/PMC6411836/ /pubmed/30576517 http://dx.doi.org/10.1093/nar/gky1276 Text en © The Author(s) 2018. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Genome Integrity, Repair and Replication Hoogenboom, Wouter S Boonen, Rick A C M Knipscheer, Puck The role of SLX4 and its associated nucleases in DNA interstrand crosslink repair |
title | The role of SLX4 and its associated nucleases in DNA interstrand crosslink repair |
title_full | The role of SLX4 and its associated nucleases in DNA interstrand crosslink repair |
title_fullStr | The role of SLX4 and its associated nucleases in DNA interstrand crosslink repair |
title_full_unstemmed | The role of SLX4 and its associated nucleases in DNA interstrand crosslink repair |
title_short | The role of SLX4 and its associated nucleases in DNA interstrand crosslink repair |
title_sort | role of slx4 and its associated nucleases in dna interstrand crosslink repair |
topic | Genome Integrity, Repair and Replication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6411836/ https://www.ncbi.nlm.nih.gov/pubmed/30576517 http://dx.doi.org/10.1093/nar/gky1276 |
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