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Human Rvb1/Tip49 is required for the histone acetyltransferase activity of Tip60/NuA4 and for the downregulation of phosphorylation on H2AX after DNA damage.

The role of chromatin-remodeling factors in transcription is well established, but the link between chromatin-remodeling complexes and DNA repair remains unexplored. Human Rvb1 and Rvb2 are highly conserved AAA(+) ATP binding proteins that are part of various chromatin-remodeling complexes, such as Ino80, SNF2-related CBP activator protein (SRCAP), and Tip60/NuA4 complexes, but their molecular function is unclear. The depletion of Rvb1 increases the amount and persistence of phosphorylation on chromatin-associated H2AX after the exposure of cells to UV irradiation or to mitomycin C, cisplatin, camptothecin, or etoposide, without increasing the amount of DNA damage. Tip60 depletion, but not Ino80 or SRCAP depletion, mimics the effect of Rvb1 depletion on H2AX phosphorylation. Rvb1 is required for the histone acetyltransferase (HAT) activity of the Tip60 complex, and histone H4 acetylation is required prior to the dephosphorylation of phospho-H2AX. Thus, Rvb1 is critical for the dephosphorylation of phospho-H2AX due to the role of Rvb1 in maintaining the HAT activity of Tip60/NuA4, implicating the Rvb1-Tip60 complex in the chromatin-remodeling response of cells after DNA damage.

Pubmed ID: 18285460

Authors

  • Jha S
  • Shibata E
  • Dutta A

Journal

Molecular and cellular biology

Publication Data

April 27, 2008

Associated Grants

  • Agency: NCI NIH HHS, Id: R01 CA089406
  • Agency: NCI NIH HHS, Id: R01 CA089406-07A2
  • Agency: NCI NIH HHS, Id: R01 CA89406
  • Agency: NIGMS NIH HHS, Id: R01 GM084465

Mesh Terms

  • Acetylation
  • Carrier Proteins
  • Cell Line
  • Chromatin
  • DNA
  • DNA Damage
  • DNA Helicases
  • DNA Repair
  • Down-Regulation
  • Enzyme Activation
  • Histone Acetyltransferases
  • Histones
  • Humans
  • Phenotype
  • Phosphatidylinositol 3-Kinases
  • Phosphorylation
  • Protein Binding
  • RNA, Small Interfering