title: The Fanconi anemia proteins FANCD2 and FANCJ interact and regulate each other's chromatin localization.
abstract: 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.
authors: From the Departments of Pediatrics.
authors: Xiaoyong
authors: X
authors: Chen
authors: the Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, Liverpool L3 9TA, United Kingdom.
authors: James B
authors: JB
authors: Wilson
authors: From the Departments of Pediatrics.
authors: Patricia
authors: P
authors: McChesney
authors: From the Departments of Pediatrics.
authors: Stacy A
authors: SA
authors: Williams
authors: Molecular Biophysics and Biochemistry, Yale University School of Medicine, Section of Hematology/Oncology, New Haven, Connecticut 06520.
authors: Youngho
authors: Y
authors: Kwon
authors: Molecular Biophysics and Biochemistry, Yale University School of Medicine, Section of Hematology/Oncology, New Haven, Connecticut 06520.
authors: Simonne
authors: S
authors: Longerich
authors: the Department of Biochemistry, Institute of Integrative Biology, University of Liverpool, Liverpool L69 7ZB, United Kingdom, and.
authors: Andrew S
authors: AS
authors: Marriott
authors: Molecular Biophysics and Biochemistry, Yale University School of Medicine, Section of Hematology/Oncology, New Haven, Connecticut 06520.
authors: Patrick
authors: P
authors: Sung
authors: the Department of Biochemistry, Institute of Integrative Biology, University of Liverpool, Liverpool L69 7ZB, United Kingdom, and.
authors: Nigel J
authors: NJ
authors: Jones
authors: From the Departments of Pediatrics, Pathology, and gary.kupfer@yale.edu.
authors: Gary M
authors: GM
authors: Kupfer
mesh_terms: D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism*; D002843:Chromatin / Q000235:genetics*; D004249:DNA Damage / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D005199:Fanconi Anemia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D052236:Fanconi Anemia Complementation Group D2 Protein / Q000235:genetics / Q000378:metabolism*; D051856:Fanconi Anemia Complementation Group Proteins / Q000235:genetics / Q000378:metabolism*; D042822:Genomic Instability; D006801:Humans; D009154:Mutation; D011485:Protein Binding
chemical_list: C102108:BACH1 protein, human; D050976:Basic-Leucine Zipper Transcription Factors; D002843:Chromatin; D004268:DNA-Binding Proteins; C499905:FANCD2 protein, human; D052236:Fanconi Anemia Complementation Group D2 Protein; D051856:Fanconi Anemia Complementation Group Proteins
keywords: Cancer Biology; DNA Damage Response; DNA Repair; FANCD2; FANCJ; Fanconi Anemia; Genetic Disease; Genomic Instability