In vivo destabilization and functional defects of the xeroderma pigmentosum C protein caused by a pathogenic missense mutation.

ABSTRACT: Xeroderma pigmentosum group C (XPC) protein plays an essential role in DNA damage recognition in mammalian global genome nucleotide excision repair (NER). Here, we analyze the functional basis of NER inactivation caused by a single amino acid substitution (Trp to Ser at position 690) in XPC, previously identified in the XPC patient XP13PV. The Trp690Ser change dramatically affects the in vivo stability of the XPC protein, thereby causing a significant reduction of its steady-state level in XP13PV fibroblasts. Despite normal heterotrimeric complex formation and physical interactions with other NER factors, the mutant XPC protein lacks binding affinity for both undamaged and damaged DNA. Thus, this single amino acid substitution is sufficient to compromise XPC function through both quantitat

SUBMITTER: Yasuda G 

PROVIDER: S-EPMC2099227 | biostudies-literature | 2007 Oct

REPOSITORIES: biostudies-literature