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A FANCD2 domain activates Tip60-dependent apoptosis

Authors

  • James Hejna,

    1. Department of Molecular and Medical Genetics, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 972393098, U.S.A.
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  • Donald Bruun,

    1. Department of Molecular and Medical Genetics, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 972393098, U.S.A.
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    • 1120 Haring Hall, One Shields Ave., Davis, CA 95616, U.S.A.

  • Daniel Pauw,

    1. Department of Molecular and Medical Genetics, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 972393098, U.S.A.
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  • Robb E. Moses

    Corresponding author
    1. Department of Molecular and Medical Genetics, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 972393098, U.S.A.
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email mosesr@ohsu.edu

Abstract

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.

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