2006/04/03 by Paul C. Blainey, Antoine M. van Oijen, Anirban Banerjee +2 · 2 citations
Biochemistry, Genetics and Molecular Biology · Engineering · #Diffusion and Search Dynamics #DNA and Nucleic Acid Chemistry #Nanopore and Nanochannel Transport Studies
paper · doi:10.1073/pnas.0509723103
openalex publication_date 2006/04/03 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01
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 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.