The Fanconi anemia proteins FANCD2 and FANCJ interact and regulate each other's chromatin localization.
J Biol Chem
; 289(37): 25774-82, 2014 Sep 12.
Article
en En
| MEDLINE
| ID: mdl-25070891
Fanconi anemia is a genetic disease resulting in bone marrow failure, birth defects, and cancer that is thought to encompass a defect in maintenance of genomic stability. Mutations in 16 genes (FANCA, B, C, D1, D2, E, F, G, I, J, L, M, N, O, P, and Q) have been identified in patients, with the Fanconi anemia subtype J (FA-J) resulting from homozygous mutations in the FANCJ gene. Here, we describe the direct interaction of FANCD2 with FANCJ. We demonstrate the interaction of FANCD2 and FANCJ in vivo and in vitro by immunoprecipitation in crude cell lysates and from fractions after gel filtration and with baculovirally expressed proteins. Mutation of the monoubiquitination site of FANCD2 (K561R) preserves interaction with FANCJ constitutively in a manner that impedes proper chromatin localization of FANCJ. FANCJ is necessary for FANCD2 chromatin loading and focus formation in response to mitomycin C treatment. Our results suggest not only that FANCD2 regulates FANCJ chromatin localization but also that FANCJ is necessary for efficient loading of FANCD2 onto chromatin following DNA damage caused by mitomycin C treatment.
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Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Unión Proteica
/
Cromatina
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Factores de Transcripción con Cremalleras de Leucina de Carácter Básico
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Proteínas del Grupo de Complementación de la Anemia de Fanconi
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Proteína del Grupo de Complementación D2 de la Anemia de Fanconi
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Anemia de Fanconi
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
J Biol Chem
Año:
2014
Tipo del documento:
Article