Ubiquitin Phosphorylation at Thr12 Modulates the DNA Damage Response. Walser et al

Published: 06-10-2020| Version 1 | DOI: 10.17632/k4fmj3nzfz.1
Contributor:
Lorenza Penengo

Description

Modification of ubiquitin by phosphorylation is a new and largely unexplored concept in the field. Here we found that ubiquitin phosphorylation at Thr12 (pUbT12) represents a novel histone mark, H2AK15pUbT12, which regulates the DNA damage response by inhibiting 53BP1-mediated DNA repair. Detectable as chromatin modification on H2AK15ub, pUbT12 accumulates in nuclear foci and is increased upon DNA damage. Mutating Thr12 prevents the removal of ubiquitin from H2AK15ub by USP51 deubiquitinating enzyme, leading to a pronounced accumulation of ubiquitinated chromatin. Chromatin modified by pUbT12 is inaccessible to 53BP1, but permissive to the homologous recombination (HR) proteins RNF169, RAD51 and BRCA1/BARD1 complex. Phosphorylation of ubiquitin at Thr12 in the chromatin context is a new histone mark – H2AK15pUbT12 – that regulates the DDR by hampering the activity of 53BP1 at damaged chromosomes.

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