Histone H2A variants alpha1-extension helix directs RNF168-mediated ubiquitination
2020-09-15
Nature Communications 11(1):May 2020 

Kelliher, Jessica L.; West, Kirk L.; Gong, Qingguo; Leung, Justin W. C.

Abstract:

Histone ubiquitination plays an important role in the DNA damage response (DDR) pathway. RNF168 catalyzes H2A and H2AX ubiquitination on lysine 13/15 (K13/K15) upon DNA damage and promotes the accrual of downstream repair factors at damaged chromatin. Here, we report that RNF168 ubiquitinates the non-canonical H2A variants H2AZ and macroH2A1/2 at the divergent N-terminal tail lysine residue. In addition to their evolutionarily conserved nucleosome acidic patch, we identify the positively charged alpha1-extension helix as essential for RNF168-mediated ubiquitination of H2A variants. Moreover, mutation of the RNF168 UMI (UIM- and MIU-related UBD) hydrophilic acidic residues abolishes RNF168-mediated ubiquitination as well as 53BP1 and BRCA1 ionizing radiation-induced foci formation. Our results reveal a juxtaposed bipartite electrostatic interaction utilized by the nucleosome to direct RNF168 orientation towards the target lysine residues in proximity to the H2A alpha1-extension helix, which plays an important role in the DDR pathway.

https://www.x-mol.com/paper/1262483118627069952?adv 


Last updated: Sep. 2020   |  Copyright © Hefei National Laboratory for Physical Sciences at the Microscale  |  Top  |  Site Map