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FANCI-FANCD2 stabilizes the RAD51-DNA complex by binding RAD51 and protects the 5′-DNA end
The FANCI-FANCD2 (I-D) complex is considered to work with RAD51 to protect the damaged DNA in the stalled replication fork. However, the means by which this DNA protection is accomplished have remained elusive. In the present study, we found that the I-D complex directly binds to RAD51, and stabiliz...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5159555/ https://www.ncbi.nlm.nih.gov/pubmed/27694619 http://dx.doi.org/10.1093/nar/gkw876 |
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author | Sato, Koichi Shimomuki, Mayo Katsuki, Yoko Takahashi, Daisuke Kobayashi, Wataru Ishiai, Masamichi Miyoshi, Hiroyuki Takata, Minoru Kurumizaka, Hitoshi |
author_facet | Sato, Koichi Shimomuki, Mayo Katsuki, Yoko Takahashi, Daisuke Kobayashi, Wataru Ishiai, Masamichi Miyoshi, Hiroyuki Takata, Minoru Kurumizaka, Hitoshi |
author_sort | Sato, Koichi |
collection | PubMed |
description | The FANCI-FANCD2 (I-D) complex is considered to work with RAD51 to protect the damaged DNA in the stalled replication fork. However, the means by which this DNA protection is accomplished have remained elusive. In the present study, we found that the I-D complex directly binds to RAD51, and stabilizes the RAD51-DNA filament. Unexpectedly, the DNA binding activity of FANCI, but not FANCD2, is explicitly required for the I-D complex-mediated RAD51-DNA filament stabilization. The RAD51 filament stabilized by the I-D complex actually protects the DNA end from nucleolytic degradation by an FA-associated nuclease, FAN1. This DNA end protection is not observed with the RAD51 mutant from FANCR patient cells. These results clearly answer the currently enigmatic question of how RAD51 functions with the I-D complex to prevent genomic instability at the stalled replication fork. |
format | Online Article Text |
id | pubmed-5159555 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-51595552016-12-16 FANCI-FANCD2 stabilizes the RAD51-DNA complex by binding RAD51 and protects the 5′-DNA end Sato, Koichi Shimomuki, Mayo Katsuki, Yoko Takahashi, Daisuke Kobayashi, Wataru Ishiai, Masamichi Miyoshi, Hiroyuki Takata, Minoru Kurumizaka, Hitoshi Nucleic Acids Res Genome Integrity, Repair and Replication The FANCI-FANCD2 (I-D) complex is considered to work with RAD51 to protect the damaged DNA in the stalled replication fork. However, the means by which this DNA protection is accomplished have remained elusive. In the present study, we found that the I-D complex directly binds to RAD51, and stabilizes the RAD51-DNA filament. Unexpectedly, the DNA binding activity of FANCI, but not FANCD2, is explicitly required for the I-D complex-mediated RAD51-DNA filament stabilization. The RAD51 filament stabilized by the I-D complex actually protects the DNA end from nucleolytic degradation by an FA-associated nuclease, FAN1. This DNA end protection is not observed with the RAD51 mutant from FANCR patient cells. These results clearly answer the currently enigmatic question of how RAD51 functions with the I-D complex to prevent genomic instability at the stalled replication fork. Oxford University Press 2016-12-15 2016-09-30 /pmc/articles/PMC5159555/ /pubmed/27694619 http://dx.doi.org/10.1093/nar/gkw876 Text en © The Author(s) 2016. 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 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 Sato, Koichi Shimomuki, Mayo Katsuki, Yoko Takahashi, Daisuke Kobayashi, Wataru Ishiai, Masamichi Miyoshi, Hiroyuki Takata, Minoru Kurumizaka, Hitoshi FANCI-FANCD2 stabilizes the RAD51-DNA complex by binding RAD51 and protects the 5′-DNA end |
title | FANCI-FANCD2 stabilizes the RAD51-DNA complex by binding RAD51 and protects the 5′-DNA end |
title_full | FANCI-FANCD2 stabilizes the RAD51-DNA complex by binding RAD51 and protects the 5′-DNA end |
title_fullStr | FANCI-FANCD2 stabilizes the RAD51-DNA complex by binding RAD51 and protects the 5′-DNA end |
title_full_unstemmed | FANCI-FANCD2 stabilizes the RAD51-DNA complex by binding RAD51 and protects the 5′-DNA end |
title_short | FANCI-FANCD2 stabilizes the RAD51-DNA complex by binding RAD51 and protects the 5′-DNA end |
title_sort | fanci-fancd2 stabilizes the rad51-dna complex by binding rad51 and protects the 5′-dna end |
topic | Genome Integrity, Repair and Replication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5159555/ https://www.ncbi.nlm.nih.gov/pubmed/27694619 http://dx.doi.org/10.1093/nar/gkw876 |
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