Structural inscrutabilities of Histone (H2BK123) monoubiquitination: A systematic review

Abstract

Histone H2B monoubiquitination in budding yeast is a highly conserved post-translational modification. It is involved in normal functions of the cells like DNA Repair, RNA Pol II activation, trans-histone H3K and H79K methylation, meiosis, vesicle budding, etc. Deregulation of H2BK123ub can lead to the activation of proto-oncogenes and is also linked to neurodegenerative and heart diseases. Recent discoveries have enhanced the mechanistic underpinnings of H2BK123ub. For the first time, the Rad6's acidic tail has been implicated in histone recognition and interaction with Bre1's RBD domain. The non-canonical backside of Rad6 showed inhibition in polyubiquitination activity. Bre1 domains RBD and RING play a role in site-specific ubiquitination. The role of single Alaline residue in Rad6 activity. Understanding the mechanism of ubiquitination before moving to therapeutic applications is important. Current advancements in this field indicate the creation of novel therapeutic approaches and a foundation for further study.

Keywords: Post translational modifications; RBD; RING domain; Yeast.