Recognition of Damaged DNA for Nucleotide Excision Repair: A Correlated Motion Mechanism with a Mismatched cis-syn Thymine Dimer Lesion.
Mammalian global genomic nucleotide excision repair requires lesion recognition by XPC, whose detailed binding mechanism remains to be elucidated. Here we have delineated the dynamic molecular pathway and energetics of lesion-specific and productive binding by the Rad4/yeast XPC lesion recognition factor, as it forms the open complex [Min, J. H., and Pavletich, N. P. (2007) Nature 449, 570-575; Chen, X., et al. (2015) Nat. Commun. 6, 5849] that is required for excision. We investigated extensively a cis-syn cyclobutane pyrimidine dimer in mismatched duplex DNA, using high-level computational approaches. Our results delineate a preferred correlated motion mechanism, which provides for the first time an atomistic description of the sequence of events as Rad4 productively binds to the damaged DNA.
Hong
H
Mu
Nicholas E
NE
Geacintov
NYU-ECNU Center for Computational Chemistry at NYU Shanghai , Shanghai 200062, China.
Yingkai
Y
Zhang
Suse
S
Broyde
D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D009038:Motion; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D011740:Pyrimidine Dimers / Q000737:chemistry*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism
D004268:DNA-Binding Proteins; D011740:Pyrimidine Dimers; C490846:RAD23 protein, S cerevisiae; C493797:Rad4 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D004247:DNA