“Flexible hinge” dynamics in mismatched DNA uncovered with laser temperature-jump and fluorescence correlation spectroscopy

Abstract

Altered unwinding/bending fluctuations at DNA lesion sites are implicated as plausible mechanisms for damage sensing by DNA-repair proteins. These dynamics are expected to occur on <500-µs timescale if effective in stalling proteins as they scan DNA. Here, we measured conformational distributions and dynamics of DNA oligomers containing 3 base pair (bp) mismatched sites specifically recognized in vitro by nucleotide excision repair protein Rad4 (yeast ortholog of mammalian XPC) that recognizes diverse lesions from UV-damage or other genotoxins and initiates DNA repair.