A base-excision DNA-repair protein finds intrahelical lesion bases by fast sliding in contact with DNA
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Author
Blainey, Paul C.
Oijen, Antoine van
Banerjee, Anirban
Verdine, Gregory L.
Xie, X. Sunney
Published Version
https://doi.org/10.1073/pnas.0509723103Metadata
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Blainey, P. C., A. M. van Oijen, A. Banerjee, G. L. Verdine, and X. S. Xie. 2006. “A Base-Excision DNA-Repair Protein Finds Intrahelical Lesion Bases by Fast Sliding in Contact with DNA.” Proceedings of the National Academy of Sciences103 (15): 5752–57. https://doi.org/10.1073/pnas.0509723103.Abstract
A central mystery in the function of site-specific DNA-binding proteins is the detailed mechanism for rapid location and binding of target sites in DNA. Human oxoguanine DNA glycosylase 1 (hOgg1), for example, must search out rare 8-oxoguanine lesions to prevent transversion mutations arising from oxidative stress. Here we report high-speed imaging of single hOgg1 enzyme molecules diffusing along DNA stretched by shear flow. Salt-concentration-dependent measurements reveal that such diffusion occurs as hOgg1 slides in persistent contact with DNA. At near-physiologic pH and salt concentration, hOgg1 has a subsecond DNA-binding time and slides with a diffusion constant as high as 5 x 10(6) bp(2)/S. Such a value approaches the theoretical upper limit for one-dimensional diffusion and indicates an activation barrier for sliding of only 0.5 kcal/mol (1 kcal = 4.2 W). This nearly barrierless Brownian sliding indicates that DNA glycosylases locate lesion bases by a massively redundant search in which the enzyme selectively binds 8-oxoguanine under kinetic control.Terms of Use
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