AUTHOR=Rüthemann Peter , Balbo Pogliano Chiara , Naegeli Hanspeter 

TITLE=Global-genome Nucleotide Excision Repair Controlled by Ubiquitin/Sumo Modifiers

JOURNAL=Frontiers in Genetics

VOLUME=7

YEAR=2016

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2016.00068

DOI=10.3389/fgene.2016.00068

ISSN=1664-8021

ABSTRACT=<p>Global-genome nucleotide excision repair (GG-NER) prevents genome instability by excising a wide range of different DNA base adducts and crosslinks induced by chemical carcinogens, ultraviolet (UV) light or intracellular side products of metabolism. As a versatile damage sensor, xeroderma pigmentosum group C (XPC) protein initiates this generic defense reaction by locating the damage and recruiting the subunits of a large lesion demarcation complex that, in turn, triggers the excision of aberrant DNA by endonucleases. In the very special case of a DNA repair response to UV radiation, the function of this XPC initiator is tightly controlled by the dual action of cullin-type CRL4<sup>DDB2</sup> and sumo-targeted RNF111 ubiquitin ligases. This twofold protein ubiquitination system promotes GG-NER reactions by spatially and temporally regulating the interaction of XPC protein with damaged DNA across the nucleosome landscape of chromatin. In the absence of either CRL4<sup>DDB2</sup> or RNF111, the DNA excision repair of UV lesions is inefficient, indicating that these two ubiquitin ligases play a critical role in mitigating the adverse biological effects of UV light in the exposed skin.</p>