Evidence for intrinsic DNA dynamics and deformability in damage sensing by the Rad4/XPC nucleotide excision repair complex.

ABSTRACT: Altered DNA dynamics at lesion sites are implicated in how DNA repair proteins sense damage within genomic DNA. Using laser temperature-jump (T-jump) spectroscopy combined with cytosine-analog Förster Resonance Energy Transfer (FRET) probes that sense local DNA conformations, we measured the intrinsic dynamics of DNA containing 3 base-pair mismatches recognized in vitro by Rad4 (yeast ortholog of XPC). Rad4/XPC recognizes diverse lesions from environmental mutagens and initiates nucleotide excision repair. T-jump measurements, together with a novel and rigorous comparison with equilibrium FRET, uncovered conformational dynamics spanning multiple timescales and revealed key differences between Rad4-specific and non-specific DNA. AT-rich non-specific sites (matched or mismatched) exhibited d

SUBMITTER: Baral S 

PROVIDER: S-EPMC11724326 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature