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Apparent Directional Scanning for DNA Repair

Department of Chemistry, James Franck Institute, and Institute for Biophysical Dynamics, The University of Chicago, Chicago, Illinois

Correspondence: Address reprint requests to Aaron R. Dinner, Gordon Center for Integrative Science, 929 East 57th St., Chicago, IL 60637. Tel.: 773-702-2330; Fax: 773-834-5250; E-mail: dinner{at}uchicago.edu.

Recently it was observed that the DNA repair protein human O⁶-alkylguanine-DNA alkyltransferase repairs lesions at the 5' ends of 70-nucleotide single-stranded DNA roughly threefold more frequently than lesions at the 3' ends. Here, we introduce a coarse-grained model to show how a local asymmetry in binding kinetics (rather than thermodynamics) together with irreversible alkyl transfer can give rise to this apparent bias in sequence scanning. Exploration of the parameter space provides quantitative relationships that can be used to validate the proposed mechanism by gel-based assays.