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.

• MeSH
• adaptorové proteiny signální transdukční * antagonisté a inhibitory   genetika   metabolismus   MeSH
• apoptóza MeSH
• chromatin metabolismus   MeSH
• dvouřetězcové zlomy DNA MeSH
• HeLa buňky MeSH
• HIV genetika   MeSH
• jaderné proteiny metabolismus   MeSH
• lidé MeSH
• malá interferující RNA genetika   MeSH
• nádorové buněčné linie MeSH
• rekombinační oprava DNA * fyziologie   MeSH
• RNA interference MeSH
• transkripční faktory * antagonisté a inhibitory   genetika   metabolismus   MeSH
• transportní proteiny metabolismus   MeSH
• viabilita buněk MeSH
• Check Tag
• lidé MeSH