Histone deacetylase inhibitors decrease NHEJ both by acetylation of repair factors and trapping of PARP1 at DNA double-strand breaks in chromatin

Highlights • Histone deacetylase inhibitors (HDACi) decrease c-NHEJ. • p300/CBP inhibition decreases PARP1 acetylation, and increases c-NHEJ. • PARP1 is significantly enriched at DSBs following HDACi treatment. • PARP1 trapping by HDACi decreases access of c-NHEJ factors in chromatin. • Combination...

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Bibliographic Details
Published in:Leukemia research 2016-06, Vol.45, p.14-23
Main Authors: Robert, Carine, Nagaria, Pratik, Pawar, Nisha, Adewuyi, Adeoluwa, Gojo, Ivana, Meyers, David J, Cole, Philip A, Rassool, Feyruz V
Format: Article
Language:English
Subjects:
Acetylation
Benzamides - pharmacology
Chromatin - metabolism
DNA Breaks, Double-Stranded - drug effects
DNA End-Joining Repair - drug effects
DSB repair
HDAC
Hematology, Oncology and Palliative Medicine
Histone Deacetylase Inhibitors - pharmacology
Histone Deacetylase Inhibitors - therapeutic use
Humans
Ku Autoantigen - metabolism
Leukemia, Myeloid, Acute - drug therapy
NHEJ
PARP1
Poly (ADP-Ribose) Polymerase-1 - metabolism
Pyridines - pharmacology
Tumor Cells, Cultured
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Summary:Highlights • Histone deacetylase inhibitors (HDACi) decrease c-NHEJ. • p300/CBP inhibition decreases PARP1 acetylation, and increases c-NHEJ. • PARP1 is significantly enriched at DSBs following HDACi treatment. • PARP1 trapping by HDACi decreases access of c-NHEJ factors in chromatin. • Combination of HDACi and PARP inhibitor induces apoptotic cell death
ISSN:0145-2126
1873-5835
DOI:10.1016/j.leukres.2016.03.007