Nucleosome Acidic Patch Promotes RNF168- and RING1B/BMI1-Dependent H2AX and H2A Ubiquitination and DNA Damage Signaling

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Post-translational modifications of histones play important roles in regulating both the structure and function of chromatin. As all DNA based processes, including transcription, DNA replication and DNA repair, occur within the context of chromatin, the actual in vivo substrate of these reactions is chromatin. Thus, understanding these processes within the context of chromatin is vital for providing mechanistic insights into chromatin-based processes, including DNA damage signaling and genome maintenance. Here we identify a structure within H2A and H2AX termed the acidic patch that promotes the activity of two independent ubiquitin E3 ligase complexes, RNF168 and RING1B/BMI1, and is required for DNA damage ubiquitin signaling. We show directly in vitro and in vivo that this nucleosome structure is critical for histone H2A and H2AX ubiquitinations and the DNA damage response in cells. In addition, we engineered a novel biological tool that blocked the nucleosome acidic patch of all histone H2A species leading to the repression of the DNA damage response in cells. Collectively, DNA damage factors elicit their response not only through histone modifications such as ubiquitin but also through interactions within nucleosome surface structures to activate DNA damage signaling.

Vyšlo v časopise: Nucleosome Acidic Patch Promotes RNF168- and RING1B/BMI1-Dependent H2AX and H2A Ubiquitination and DNA Damage Signaling. PLoS Genet 10(3): e32767. doi:10.1371/journal.pgen.1004178
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004178

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