|Cancer||Cell death||Cell cycle||Cytoskeleton||Exo/endocytosis||Differentiation||Division||Organelles||Signalling||Stem cells||Trafficking|
A FANCD2 domain activates Tip60-dependent apoptosis
James Hejna, Donald Bruun1, Daniel Pauw and Robb E Moses2
Department of Molecular and Medical Genetics, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 972393098, U.S.A.
The FA (Fanconi anaemia) FANCD2 protein is pivotal in the cellular response to DNA interstrand cross-links. Establishing cells expressing exogenous FANCD2 has proven to be difficult compared with other DNA repair genes. We find that in transformed normal human fibroblasts, exogenous nuclear expression of FANCD2 induces apoptosis, dependent specifically on exons 10–13. This is the same region required for interaction with the histone acetyltransferase, Tip60. Deletion of exons 10–13 from FANCD2 N-terminal constructs (nucleotides 1–1100) eliminates the binary interaction with Tip60 and the cellular apoptotic response; moreover, cells can stably express FANCD2 at high levels if Tip60 is depleted. The results indicate that FANCD2-sponsored apoptosis requires an interaction with Tip60 and depends on Tip60.
Key words: apoptosis, Fanconi anaemia, histone acetyltransferase, interstrand cross-link repair, Tip60
Abbreviations: DSB, double-strand break, EGFP, enhanced green fluorescent protein, FA, Fanconi anaemia, FBS, fetal bovine serum, ICL, interstrand cross-linking, NLS, nuclear localization signal, siRNA, small interfering RNA
1Present address: 1120 Haring Hall, One Shields Ave., Davis, CA 95616, U.S.A.
2To whom correspondence should be addressed (email firstname.lastname@example.org).
Received 30 September 2009/28 April 2010; accepted 27 May 2010
Published as Cell Biology International Immediate Publication 27 May 2010, doi:10.1042/CBI20090251
© The Author(s) Journal compilation © 2010 Portland Press Limited