Regulation of damage recognition in mammalian global genomic nucleotide excision repair

Nucleotide excision repair operating throughout the mammalian genome plays a crucial role in the suppression of mutagenesis and carcinogenesis, which can arise from DNA lesions induced by a wide variety of genotoxic agents, such as ultraviolet light and chemical compounds. A key process of this DNA repair pathway, damage recognition, is accomplished through multiple steps including concerted actions of the damaged DNA binding factors XPC and UV-DDB, both of which are implicated in a human cancerprone genetic disorder, xeroderma pigmentosum. Accumulating evidence indicates that the expression and functions of these damage recognition factors are subject to exquisite regulation at diverse levels, including transcriptional activation, post-translational modification, complex formation, and protein degradation through ubiquitination. (C) 2009 Elsevier B.V. All rights reserved.