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Deletion of histone deacetylase 3 reveals critical roles in S phase progression and DNA damage control.

Histone deacetylases (HDACs) are enzymes that modify key residues in histones to regulate chromatin architecture, and they play a vital role in cell survival, cell-cycle progression, and tumorigenesis. To understand the function of Hdac3, a critical component of the N-CoR/SMRT repression complex, a conditional allele of Hdac3 was engineered. Cre-recombinase-mediated inactivation of Hdac3 led to a delay in cell-cycle progression, cell-cycle-dependent DNA damage, and apoptosis in mouse embryonic fibroblasts (MEFs). While no overt defects in mitosis were observed in Hdac3-/- MEFs, including normal H3Ser10 phosphorylation, DNA damage was observed in Hdac3-/- interphase cells, which appears to be associated with defective DNA double-strand break repair. Moreover, we noted that Hdac3-/- MEFs were protected from DNA damage when quiescent, which may provide a mechanistic basis for the action of HDAC inhibitors on cycling tumor cells.

Pubmed ID: 18406327


  • Bhaskara S
  • Chyla BJ
  • Amann JM
  • Knutson SK
  • Cortez D
  • Sun ZW
  • Hiebert SW


Molecular cell

Publication Data

April 11, 2008

Associated Grants

  • Agency: NCI NIH HHS, Id: P30-CA68485
  • Agency: NIDDK NIH HHS, Id: P30DK58404
  • Agency: NCI NIH HHS, Id: R01 CA064140
  • Agency: NCI NIH HHS, Id: R01 CA064140-15
  • Agency: NCI NIH HHS, Id: R01 CA077274
  • Agency: NCI NIH HHS, Id: R01 CA077274-10
  • Agency: NCI NIH HHS, Id: R01 CA109355
  • Agency: NCI NIH HHS, Id: R01-CA64140
  • Agency: NCI NIH HHS, Id: R01-CA77274
  • Agency: NCI NIH HHS, Id: R21 CA132010
  • Agency: NCI NIH HHS, Id: R21 CA132010-02

Mesh Terms

  • Animals
  • Apoptosis
  • Caffeine
  • Cells, Cultured
  • DNA Damage
  • DNA Repair
  • Fibroblasts
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Histone Deacetylases
  • Humans
  • Mice
  • Mice, Knockout
  • Mitosis
  • NIH 3T3 Cells
  • Neoplasms
  • Oligonucleotide Array Sequence Analysis
  • Phenotype
  • Phosphodiesterase Inhibitors
  • Radiation, Ionizing
  • S Phase