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The Bre1/Rad6 machinery: writing the central histone ubiquitin mark on H2B and beyond.

Zhi-Heng DengHua-Song AiCheng-Piao LuJia-Bin Li
Published in: Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology (2020)
Mono-ubiquitination on H2B (H2Bub1) is an evolutionarily conserved histone post-translational modification implicated in various important physiological processes including DNA replication, transcription activation, and DNA damage repair. The Bre1/Rad6 ubiquitination machinery is currently considered to be the sole writer of H2Bub1, but the mechanistic basis by which it operates is unclear. Recently, the RING-type E3 ligase Bre1 was proposed to associate with the E2 enzyme Rad6 through a novel interaction between Bre1 RBD (Rad6 binding domain) and Rad6; and the RING domain of Bre1 that is responsible for the nucleosomal acidic patch binding also interacts with Rad6 to stimulate its catalytic activity. Recent discoveries have yielded evidence for the phenomenon of liquid-liquid phase separation in the context of H2Bub1, and its regulation by other histone post-translational modifications. This review summarizes current knowledge about Bre1/Rad6-mediated H2B ubiquitination, including the physiological functions and the molecular basis for writing and regulation of this central histone ubiquitin mark. Possible models for the Bre1/Rad6 machinery bound to nucleosomes bearing different modifications in the writing step are also disclosed.
Keyphrases
  • dna damage
  • dna repair
  • dna methylation
  • oxidative stress
  • healthcare
  • transcription factor
  • small molecule
  • dna binding
  • gene expression