Human CRL4DDB2 ubiquitin ligase preferentially regulates post-repair chromatin restoration of H3K56Ac through recruitment of histone chaperon CAF-1
Metrics: PDF 1747 views | HTML 2351 views | ?
Qianzheng Zhu1, Shengcai Wei1, Nidhi Sharma1, Gulzar Wani1, Jinshan He1 and Altaf A. Wani1,2,3
1Department of Radiology, The Ohio State University, Columbus, 43210, OH
2Department of Molecular and Cellular Biochemistry, The Ohio State University, Columbus, 43210, OH
3James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, 43210, OH
Qianzheng Zhu, email: [email protected]
Altaf A. Wani, email: [email protected]
Keywords: acetylated histone H3 lysine 56 (H3K56Ac), chromatin assembly, damaged DNA binding protein 2 (DDB2), CRL4DDB2 ubiquitin ligase, CUL4A and CAF-1
Received: August 23, 2017 Accepted: September 30, 2017 Published: October 17, 2017
Acetylated histone H3 lysine 56 (H3K56Ac) diminishes in response to DNA damage but is restored following DNA repair. Here, we report that CRL4DDB2 ubiquitin ligase preferentially regulates post-repair chromatin restoration of H3K56Ac through recruitment of histone chaperon CAF-1. We show that H3K56Ac accumulates at DNA damage sites. The restoration of H3K56Ac but not H3K27Ac, H3K18Ac and H3K14Ac depends on CAF-1 function, whereas all these acetylations are mediated by CBP/p300. The CRL4DDB2 components, DDB1, DDB2 and CUL4A, are also required for maintaining the H3K56Ac and H3K9Ac level in chromatin, and for restoring H3K56Ac following induction of DNA photolesions and strand breaks. Depletion of CUL4A decreases the recruitment of CAF-1 p60 and p150 to ultraviolet radiation- and phleomycin-induced DNA damage. Neddylation inhibition renders CRL4DDB2 inactive, decreases H3K56Ac level, diminishes CAF-1 recruitment and prevents H3K56Ac restoration. Mutation in the PIP box of DDB2 compromises its capability to elevate the H3K56Ac level but does not affect XPC ubiquitination. These results demonstrated a function of CRL4DDB2 in differential regulation of histone acetylation in response to DNA damage, suggesting a novel role of CRL4DDB2 in repair-driven chromatin assembly.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.