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Histone H3 and H4 ubiquitylation by the CUL4-DDB-ROC1 ubiquitin ligase facilitates cellular response to DNA damage.

Posttranslational histone modifications play important roles in transcription and other chromatin-based processes. Compared to acetylation, methylation, and phosphorylation, very little is known about the function of histone ubiquitylation. Here, we report the purification and functional characterization of a histone H3 and H4 ubiquitin ligase complex, CUL4-DDB-ROC1. We demonstrate that CUL4-DDB-ROC1-mediated H3 and H4 ubiquitylation occurs both in vitro and in vivo. Importantly, CUL4-DDB-ROC1-mediated H3 and H4 ubiquitylation is regulated by UV irradiation. Reduction of histone H3 and H4 ubiquitylation by knockdown of CUL4A impairs recruitment of the repair protein XPC to the damaged foci and inhibits the repair process. Biochemical studies indicate that CUL4-DDB-ROC1-mediated histone ubiquitylation weakens the interaction between histones and DNA and facilitates the recruitment of repair proteins to damaged DNA. Thus, our studies uncover CUL4-DDB-ROC1 as a histone ubiquitin ligase and demonstrate that histone H3 and H4 ubiquitylation participates in the cellular response to DNA damage.

Pubmed ID: 16678110

Authors

  • Wang H
  • Zhai L
  • Xu J
  • Joo HY
  • Jackson S
  • Erdjument-Bromage H
  • Tempst P
  • Xiong Y
  • Zhang Y

Journal

Molecular cell

Publication Data

May 5, 2006

Associated Grants

  • Agency: NIGMS NIH HHS, Id: GM68804
  • Agency: NCI NIH HHS, Id: P30 CA087848

Mesh Terms

  • Carrier Proteins
  • Cullin Proteins
  • DNA Damage
  • DNA-Binding Proteins
  • HeLa Cells
  • Histones
  • Humans
  • Nucleosomes
  • RNA, Small Interfering
  • Ubiquitin
  • Ubiquitin-Protein Ligase Complexes
  • Ultraviolet Rays