Histone H3 and H4 ubiquitylation by the CUL4-DDB-ROC1 ubiquitin ligase facilitates cellular response to DNA damage Journal Article
| Authors: | Wang, H.; Zhai, L.; Xu, J.; Joo, H. Y.; Jackson, S.; Erdjument-Bromage, H.; Tempst, P.; Xiong, Y.; Zhang, Y. |
| Article Title: | Histone H3 and H4 ubiquitylation by the CUL4-DDB-ROC1 ubiquitin ligase facilitates cellular response to DNA damage |
| Abstract: | 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. © 2006 Elsevier Inc. All rights reserved. |
| Keywords: | carrier protein; unclassified drug; dna binding protein; human cell; genetics; dna-binding proteins; ubiquitin; ultraviolet radiation; proteins; metabolism; dna damage; complex formation; dna repair; ubiquitin protein ligase; protein; small interfering rna; rna, small interfering; in vivo study; in vitro study; hela cell; hela cells; radiation exposure; dna; protein processing; ubiquitination; enzyme analysis; histone; histone h3; carrier proteins; ultraviolet rays; isolation and purification; histones; enzyme purification; cullin; cullin proteins; secretion; protein dna interaction; ultraviolet irradiation; nucleosome; nucleosomes; histone h4; ubiquitin-protein ligase complexes; cul4 protein; ddb protein; roc1 protein; cul4a protein, human; ddb1 protein, human; rbx1 protein, human |
| Journal Title: | Molecular Cell |
| Volume: | 22 |
| Issue: | 3 |
| ISSN: | 1097-2765 |
| Publisher: | Cell Press |
| Date Published: | 2006-05-05 |
| Start Page: | 383 |
| End Page: | 394 |
| Language: | English |
| DOI: | 10.1016/j.molcel.2006.03.035 |
| PUBMED: | 16678110 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 167" - "Export Date: 4 June 2012" - "CODEN: MOCEF" - "Source: Scopus" |
