Histone deacetylases 9 and 10 are required for homologous recombination.
We tested the role of histone deacetylases (HDACs) in the homologous recombination process. A tissue-culture based homology-directed repair assay was used in which repair of a double-stranded break by homologous recombination results in gene conversion of an inactive GFP allele to an active GFP gene. Our rationale was that hyperacetylation caused by HDAC inhibitor treatment would increase chromatin accessibility to repair factors, thereby increasing homologous recombination. Contrary to expectation, treatment of cells with the inhibitors significantly reduced homologous recombination activity. Using RNA interference to deplete each HDAC, we found that depletion of either HDAC9 or HDAC10 specifically inhibited homologous recombination. By assaying for sensitivity of cells to the interstrand cross-linker mitomycin C, we found that treatment of cells with HDAC inhibitors or depletion of HDAC9 or HDAC10 resulted in increased sensitivity to mitomycin C. Our data reveal an unanticipated function of HDAC9 and HDAC10 in the homologous recombination process.
From the Department of Biomedical Informatics and.
Shweta
S
Kotian
Biomedical Informatics Shared Resource, The Ohio State University Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210 and.
Sandhya
S
Liyanarachchi
the Section of Haemato-Oncology, Institute for Cancer Research, Sutton, Surrey SM2 5NG, United Kingdom.
Arthur
A
Zelent
From the Department of Biomedical Informatics and. Electronic address: jeffrey.parvin@osumc.edu.
Jeffrey D
JD
Parvin
D000107:Acetylation / Q000187:drug effects; D000477:Alkylating Agents / Q000494:pharmacology; D006367:HeLa Cells; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016685:Mitomycin / Q000494:pharmacology; D034622:RNA Interference; D011995:Recombination, Genetic / Q000187:drug effects / Q000502:physiology*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*
D000477:Alkylating Agents; D012097:Repressor Proteins; D016685:Mitomycin; C447828:HDAC10 protein, human; C486544:HDAC9 protein, human; D006655:Histone Deacetylases
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