DOI: 10.1073/pnas.0509723103. A base-excision DNA-repair protein finds intrahelical lesion bases by fast sliding in contact with DNA

A base-excision DNA-repair protein finds intrahelical lesion bases by fast sliding in contact with DNA

10.1073/pnas.0509723103

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

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 × 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 kJ). 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.

Bibliography

Blainey, P. C., van Oijen, A. M., Banerjee, A., Verdine, G. L., & Xie, X. S. (2006). A base-excision DNA-repair protein finds intrahelical lesion bases by fast sliding in contact with DNA. Proceedings of the National Academy of Sciences, 103(15), 5752â5757.

Authors 5

Paul C. Blainey (first)
Antoine M. van Oijen (additional)
Anirban Banerjee (additional)
Gregory L. Verdine (additional)
X. Sunney Xie (additional)

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Dates

Type	When
Created	19 years, 4 months ago (April 3, 2006, 8:35 p.m.)
Deposited	3 years, 4 months ago (April 12, 2022, 10:06 a.m.)
Indexed	1 month, 3 weeks ago (July 3, 2025, 9:31 a.m.)
Issued	19 years, 4 months ago (April 11, 2006)
Published	19 years, 4 months ago (April 11, 2006)
Published Online	19 years, 4 months ago (April 11, 2006)
Published Print	19 years, 4 months ago (April 11, 2006)

Funders 0

None

BibTeX

@article{Blainey_2006, title={A base-excision DNA-repair protein finds intrahelical lesion bases by fast sliding in contact with DNA}, volume={103}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.0509723103}, DOI={10.1073/pnas.0509723103}, number={15}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Blainey, Paul C. and van Oijen, Antoine M. and Banerjee, Anirban and Verdine, Gregory L. and Xie, X. Sunney}, year={2006}, month=apr, pages={5752–5757} }

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