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

M Daugaard, A Baude, K Fugger, LK Povlsen, H Beck, CS Sorensen, NH Petersen, PH Sorensen, C Lukas, J Bartek, J Lukas, M Rohde, M Jaattela

. 2012 ; 19 (8) : 803-810.

Jazyk angličtina Země Spojené státy americké

Perzistentní odkaz   https://www.medvik.cz/link/bmc14072955
E-zdroje Online Plný text

NLK ProQuest Central od 2004-01-01 do Před 1 rokem
Medline Complete (EBSCOhost) od 2004-01-01 do 2015-11-30
Health & Medicine (ProQuest) od 2004-01-01 do Před 1 rokem

Odkazy

PubMed 22773103
DOI 10.1038/nsmb.2314
Knihovny.cz E-zdroje

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.

Citace poskytuje Crossref.org

Bibliografie atd.

Literatura

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