The role of UV-DDB in processing 8-oxoguanine during base excision repair

Recent data from our laboratory has shown that the nucleotide excision repair (NER) proteins UV-damaged DNA-binding protein (UV-DDB), xeroderma pigmentosum group C (XPC), and xeroderma pigmentosum group A (XPA) play important roles in the processing of 8-oxoG. This review first discusses biochemical studies demonstrating how UV-DDB stimulates human 8-oxoG glycosylase (OGG1), MUTYH, and apurinic/apyrimidinic (AP) endonuclease (APE1) to increase their turnover at damage sites. We further discuss our single-molecule studies showing that UV-DDB associates with these proteins at abasic moieties on DNA damage arrays. Data from cell experiments are then described showing that UV-DDB interacts with OGG1 at sites of 8-oxoG. Finally, since many glycosylases are inhibited from working on damage in the context of chromatin, we present a working model of how UV-DDB may be the first responder to alter the structure of damage containing-nucleosomes to allow access by base excision repair (BER) enzymes.