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Defective FANCI Binding by a Fanconi Anemia-Related FANCD2 Mutant
FANCD2 is a product of one of the genes associated with Fanconi anemia (FA), a rare recessive disease characterized by bone marrow failure, skeletal malformations, developmental defects, and cancer predisposition. FANCD2 forms a complex with FANCI (ID complex) and is monoubiquitinated, which facilit...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260917/ https://www.ncbi.nlm.nih.gov/pubmed/25489943 http://dx.doi.org/10.1371/journal.pone.0114752 |
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author | Sato, Koichi Ishiai, Masamichi Takata, Minoru Kurumizaka, Hitoshi |
author_facet | Sato, Koichi Ishiai, Masamichi Takata, Minoru Kurumizaka, Hitoshi |
author_sort | Sato, Koichi |
collection | PubMed |
description | FANCD2 is a product of one of the genes associated with Fanconi anemia (FA), a rare recessive disease characterized by bone marrow failure, skeletal malformations, developmental defects, and cancer predisposition. FANCD2 forms a complex with FANCI (ID complex) and is monoubiquitinated, which facilitates the downstream interstrand crosslink (ICL) repair steps, such as ICL unhooking and nucleolytic end resection. In the present study, we focused on the chicken FANCD2 (cFANCD2) mutant harboring the Leu234 to Arg (L234R) substitution. cFANCD2 L234R corresponds to the human FANCD2 L231R mutation identified in an FA patient. We found that cFANCD2 L234R did not complement the defective ICL repair in FANCD2(−/−) DT40 cells. Purified cFANCD2 L234R did not bind to chicken FANCI, and its monoubiquitination was significantly deficient, probably due to the abnormal ID complex formation. In addition, the histone chaperone activity of cFANCD2 L234R was also defective. These findings may explain some aspects of Fanconi anemia pathogenesis by a FANCD2 missense mutation. |
format | Online Article Text |
id | pubmed-4260917 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-42609172014-12-15 Defective FANCI Binding by a Fanconi Anemia-Related FANCD2 Mutant Sato, Koichi Ishiai, Masamichi Takata, Minoru Kurumizaka, Hitoshi PLoS One Research Article FANCD2 is a product of one of the genes associated with Fanconi anemia (FA), a rare recessive disease characterized by bone marrow failure, skeletal malformations, developmental defects, and cancer predisposition. FANCD2 forms a complex with FANCI (ID complex) and is monoubiquitinated, which facilitates the downstream interstrand crosslink (ICL) repair steps, such as ICL unhooking and nucleolytic end resection. In the present study, we focused on the chicken FANCD2 (cFANCD2) mutant harboring the Leu234 to Arg (L234R) substitution. cFANCD2 L234R corresponds to the human FANCD2 L231R mutation identified in an FA patient. We found that cFANCD2 L234R did not complement the defective ICL repair in FANCD2(−/−) DT40 cells. Purified cFANCD2 L234R did not bind to chicken FANCI, and its monoubiquitination was significantly deficient, probably due to the abnormal ID complex formation. In addition, the histone chaperone activity of cFANCD2 L234R was also defective. These findings may explain some aspects of Fanconi anemia pathogenesis by a FANCD2 missense mutation. Public Library of Science 2014-12-09 /pmc/articles/PMC4260917/ /pubmed/25489943 http://dx.doi.org/10.1371/journal.pone.0114752 Text en © 2014 Sato et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Sato, Koichi Ishiai, Masamichi Takata, Minoru Kurumizaka, Hitoshi Defective FANCI Binding by a Fanconi Anemia-Related FANCD2 Mutant |
title | Defective FANCI Binding by a Fanconi Anemia-Related FANCD2 Mutant |
title_full | Defective FANCI Binding by a Fanconi Anemia-Related FANCD2 Mutant |
title_fullStr | Defective FANCI Binding by a Fanconi Anemia-Related FANCD2 Mutant |
title_full_unstemmed | Defective FANCI Binding by a Fanconi Anemia-Related FANCD2 Mutant |
title_short | Defective FANCI Binding by a Fanconi Anemia-Related FANCD2 Mutant |
title_sort | defective fanci binding by a fanconi anemia-related fancd2 mutant |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260917/ https://www.ncbi.nlm.nih.gov/pubmed/25489943 http://dx.doi.org/10.1371/journal.pone.0114752 |
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