Chapter 5 - Structure and Biochemistry of the Polycomb Repressive Complex 1 Ubiquitin Ligase Module

Abstract

Polycomb repressive complex 1 (PRC1) is the E3 ubiquitin ligase responsible for the majority of ubiquitin incorporation at the C-terminus of histone H2A (H2A) (lysines 118/119). Accordingly, PRC1 ligase function has been the subject of recent biochemical and structural studies. The E3 activity resides in a heterodimer of Really interesting new gene (RING) domains. One of these RINGs is present at the N-terminus of the Ring1 subunit and is the catalytically active, E2-binding RING. The second, “inactive” RING is present in the N-terminus of one of six (in human) Polycomb group (PcG) RING Finger (PCGF)-family subunits. The PCGF RING both stabilizes the active RING and influences nucleosome substrate binding and activity of the heterodimer. While biochemical aspects of ligase function are now reasonably clear, much ongoing work is focused on understanding which of the PRC1 variants (canonical or noncanonical) is most important in introducing this mark to target loci and on better defining the biological function of H2A ubiquitination.