LEDGF (p75) Promotes DNA-end Resection and Homologous Recombination

Overview

Journal Nat Struct Mol Biol

Specialties Cell Biology
Molecular Biology

Date 2012 Jul 10

PMID 22773103

Citations 115

Authors

Mads Daugaard

Annika Baude

Kasper Fugger

Lou Klitgaard Povlsen

Halfdan Beck

Claus Storgaard Sorensen

Nikolaj H T Petersen

Poul H B Sorensen

Claudia Lukas

Jiri Bartek

Jiri Lukas

Mikkel Rohde

Marja Jaattela

Affiliations

Soon will be listed here.

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.

Citing Articles

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