The Fanconi anemia proteins FANCD2 and FANCJ interact and regulate each other's chromatin localization.

X Chen, J Wilson, P McChesney, SA Williams, Y Kwon, S Longerich, Andrew Marriott, P Sung, NJ Jones, GM Kupfer

Research output: Contribution to journalArticle

14 Citations (Scopus)
75 Downloads (Pure)

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.
Original languageEnglish
Pages (from-to)25774-25782
JournalThe Journal of Biological Chemistry
Volume289
Issue number37
DOIs
Publication statusE-pub ahead of print - 28 Jul 2014

Fingerprint Dive into the research topics of 'The Fanconi anemia proteins FANCD2 and FANCJ interact and regulate each other's chromatin localization.'. Together they form a unique fingerprint.

  • Cite this

    Chen, X., Wilson, J., McChesney, P., Williams, SA., Kwon, Y., Longerich, S., Marriott, A., Sung, P., Jones, NJ., & Kupfer, GM. (2014). The Fanconi anemia proteins FANCD2 and FANCJ interact and regulate each other's chromatin localization. The Journal of Biological Chemistry, 289(37), 25774-25782. https://doi.org/10.1074/jbc.M114.552570