Histone deacetylases 9 and 10 are required for homologous recombination

Shweta Kotian, Sandhya Liyanarachchi, Arthur Z Zelent, Jeffrey D. Parvin

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)7722-7726
Number of pages5
JournalJournal of Biological Chemistry
Volume286
Issue number10
DOIs
StatePublished - Mar 11 2011
Externally publishedYes

Fingerprint

Histone Deacetylases
Homologous Recombination
Repair
Mitomycin
Cells
Gene Conversion
Tissue culture
Chromatin
Assays
Genes
RNA
RNA Interference
Alleles

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Kotian, S., Liyanarachchi, S., Zelent, A. Z., & Parvin, J. D. (2011). Histone deacetylases 9 and 10 are required for homologous recombination. Journal of Biological Chemistry, 286(10), 7722-7726. https://doi.org/10.1074/jbc.C110.194233

Histone deacetylases 9 and 10 are required for homologous recombination. / Kotian, Shweta; Liyanarachchi, Sandhya; Zelent, Arthur Z; Parvin, Jeffrey D.

In: Journal of Biological Chemistry, Vol. 286, No. 10, 11.03.2011, p. 7722-7726.

Research output: Contribution to journalArticle

Kotian, S, Liyanarachchi, S, Zelent, AZ & Parvin, JD 2011, 'Histone deacetylases 9 and 10 are required for homologous recombination', Journal of Biological Chemistry, vol. 286, no. 10, pp. 7722-7726. https://doi.org/10.1074/jbc.C110.194233
Kotian, Shweta ; Liyanarachchi, Sandhya ; Zelent, Arthur Z ; Parvin, Jeffrey D. / Histone deacetylases 9 and 10 are required for homologous recombination. In: Journal of Biological Chemistry. 2011 ; Vol. 286, No. 10. pp. 7722-7726.
@article{29d1b6a811394341a01492ff1f432920,
title = "Histone deacetylases 9 and 10 are required for homologous recombination",
abstract = "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.",
author = "Shweta Kotian and Sandhya Liyanarachchi and Zelent, {Arthur Z} and Parvin, {Jeffrey D.}",
year = "2011",
month = "3",
day = "11",
doi = "10.1074/jbc.C110.194233",
language = "English (US)",
volume = "286",
pages = "7722--7726",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "10",

}

TY - JOUR

T1 - Histone deacetylases 9 and 10 are required for homologous recombination

AU - Kotian, Shweta

AU - Liyanarachchi, Sandhya

AU - Zelent, Arthur Z

AU - Parvin, Jeffrey D.

PY - 2011/3/11

Y1 - 2011/3/11

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=79953157671&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79953157671&partnerID=8YFLogxK

U2 - 10.1074/jbc.C110.194233

DO - 10.1074/jbc.C110.194233

M3 - Article

VL - 286

SP - 7722

EP - 7726

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 10

ER -