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...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4260917?pdf=render |
| _version_ | 1818164269181566976 |
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| author | Koichi Sato Masamichi Ishiai Minoru Takata Hitoshi Kurumizaka |
| author_facet | Koichi Sato Masamichi Ishiai Minoru Takata Hitoshi Kurumizaka |
| author_sort | Koichi Sato |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-11T17:02:46Z |
| format | Article |
| id | doaj.art-1f69498f0314406c843f9503266721b0 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T17:02:46Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-1f69498f0314406c843f9503266721b02022-12-22T00:57:47ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-01912e11475210.1371/journal.pone.0114752Defective FANCI binding by a fanconi anemia-related FANCD2 mutant.Koichi SatoMasamichi IshiaiMinoru TakataHitoshi KurumizakaFANCD2 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.http://europepmc.org/articles/PMC4260917?pdf=render |
| spellingShingle | Koichi Sato Masamichi Ishiai Minoru Takata Hitoshi Kurumizaka Defective FANCI binding by a fanconi anemia-related FANCD2 mutant. PLoS ONE |
| 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 |
| url | http://europepmc.org/articles/PMC4260917?pdf=render |
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