LEDGF (p75) promotes DNA-end resection and homologous recombination
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LEDGF (p75) promotes DNA-end resection and homologous recombination. / 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; Jaattela, Marja.
In: Nature Structural & Molecular Biology, Vol. 19, No. 8, 08.2012, p. 803-810.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - LEDGF (p75) promotes DNA-end resection and homologous recombination
AU - Daugaard, Mads
AU - Baude, Annika
AU - Fugger, Kasper
AU - Povlsen, Lou Klitgaard
AU - Beck, Halfdan
AU - Sørensen, Claus Storgaard
AU - Petersen, Nikolaj H T
AU - Sorensen, Poul H B
AU - Lukas, Claudia
AU - Bartek, Jiri
AU - Lukas, Jiri
AU - Rohde, Mikkel
AU - Jaattela, Marja
PY - 2012/8
Y1 - 2012/8
N2 - 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.
AB - 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.
U2 - 10.1038/nsmb.2314
DO - 10.1038/nsmb.2314
M3 - Journal article
C2 - 22773103
VL - 19
SP - 803
EP - 810
JO - Nature Structural and Molecular Biology
JF - Nature Structural and Molecular Biology
SN - 1545-9993
IS - 8
ER -
ID: 38488448