LEDGF (p75) promotes DNA-end resection and homologous recombination - PubMed (original) (raw)

doi: 10.1038/nsmb.2314. Epub 2012 Jul 8.

Annika Baude, Kasper Fugger, Lou Klitgaard Povlsen, Halfdan Beck, Claus Storgaard Sørensen, Nikolaj H T Petersen, Poul H B Sorensen, Claudia Lukas, Jiri Bartek, Jiri Lukas, Mikkel Rohde, Marja Jäättelä

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LEDGF (p75) promotes DNA-end resection and homologous recombination

Mads Daugaard et al. Nat Struct Mol Biol. 2012 Aug.

Abstract

Lens epithelium-derived growth factor p75 splice variant (LEDGF) is a chromatin-binding protein known for its antiapoptotic activity and ability to direct human immunodeficiency virus into active transcription units. Here we show that LEDGF promotes the repair of DNA double-strand breaks (DSBs) by the homologous recombination repair pathway. Depletion of LEDGF impairs the recruitment of C-terminal binding protein interacting protein (CtIP) to DNA DSBs and the subsequent CtIP-dependent DNA-end resection. LEDGF is constitutively associated with chromatin through its Pro-Trp-Trp-Pro (PWWP) domain that binds preferentially to epigenetic methyl-lysine histone markers characteristic of active transcription units. LEDGF binds CtIP in a DNA damage-dependent manner, thereby enhancing its tethering to the active chromatin and facilitating its access to DNA DSBs. These data highlight the role of PWWP-domain proteins in DNA repair and provide a molecular explanation for the antiapoptotic and cancer cell survival-activities of LEDGF.

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