Sequence specificity, energetics and mechanism of mismatch recognition by DNA damage sensing protein Rad4/XPC.

ABSTRACT: The ultraviolet (UV) radiation-induced DNA lesions play a causal role in many prevalent genetic skin-related diseases and cancers. The damage sensing protein Rad4/XPC specifically recognizes and repairs these lesions with high fidelity and safeguards genome integrity. Despite considerable progress, the mechanistic details of the mode of action of Rad4/XPC in damage recognition remain obscure. The present study investigates the mechanism, energetics, dynamics, and the molecular basis for the sequence specificity of mismatch recognition by Rad4/XPC. We dissect the following three key molecular events that occur as Rad4/XPC tries to recognize and bind to DNA lesions/mismatches: (a) the association of Rad4/XPC with the damaged/mismatched DNA, (b) the insertion of a lesion-sensing β-hairpin of

SUBMITTER: Panigrahi A 

PROVIDER: S-EPMC7049735 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature