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- Title
LEDGF (p75) promotes DNA-end resection and homologous recombination.
- Authors
Daugaard, Mads; Baude, Annika; Fugger, Kasper; Povlsen, Lou Klitgaard; Beck, Halfdan; Sørensen, Claus Storgaard; Petersen, Nikolaj H T; Sorensen, Poul H B; Lukas, Claudia; Bartek, Jiri; Lukas, Jiri; Rohde, Mikkel; Jäättelä, Marja
- 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.
- Subjects
DNA; SURGICAL excision; GROWTH factors; HIV; DOUBLE-stranded RNA; CHROMATIN; DNA repair
- Publication
Nature Structural & Molecular Biology, 2012, Vol 19, Issue 8, p803
- ISSN
1545-9993
- Publication type
Article
- DOI
10.1038/nsmb.2314