Abstract
Chromatin is a highly organized and dynamic structure in eukaryotic cells. The change of chromatin structure is essential in many cellular processes, such as gene transcription, DNA damage repair and others. Anti-silencing function 1 (ASF1) is a histone chaperone that participates in chromatin higher-order organization and is required for appropriate chromatin assembly. In this study, we identified the E2 ubiquitin-conjugating enzyme RAD6 as an evolutionary conserved interacting protein of ASF1 in D. melanogaster and H. sapiens that promotes the turnover of ASF1A by cooperating with a well-known E3 ligase, MDM2, via ubiquitin-proteasome pathway in H. sapiens. Further functional analyses indicated that the interplay between RAD6 and ASF1A associates with tumorigenesis. Together, these data suggest that the RAD6-MDM2 ubiquitin ligase machinery is critical for the degradation of chromatin-related proteins.
Highlights
The accurate organization of chromatin from DNA and histones is essential for almost all types of life processes, such as cell proliferation, differentiation and migration
In addition to our previous work showed that the RAD6-MDM2 complex synergistically targets p53 for turnover [45,46,47,48,49], we found that ASF1A is a new and conserved target of the RAD6-MDM2 degradation machine in both Drosophila and Homo sapiens
It has been previously reported that Anti-silencing function 1 (ASF1) and Rad6 have a genetic interaction in yeast, especially after DNA damage [50]
Summary
The accurate organization of chromatin from DNA and histones is essential for almost all types of life processes, such as cell proliferation, differentiation and migration. The nucleosome is the repeat unit of chromatin and contains approximately 147 bp DNA and the core histones (H3, H4, H2A and H2B) [1,2,3,4]. These core histones form an octamer around which the DNA is wrapped. Chromatin assembly is tightly regulated and mediated by histone chaperones, which function through binding to histones [5,6,7,8]
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