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Updated: Oct 5, 2025

DNA Sequence Recognition by DNA Primase Using High-Throughput Primase Profiling
Published on: October 8, 2019
Sequence specificity in DNA binding is mainly governed by association
Emil Marklund1, Guanzhong Mao1, Jinwen Yuan1
1Department of Cell and Molecular Biology, Science for Life Laboratory, Uppsala University, Box 596, 75124, Uppsala, Sweden.
Abstract:
Sequence-specific binding of proteins to DNA is essential for accessing genetic information. We derive a model that predicts an anticorrelation between the macroscopic association and dissociation rates of DNA binding proteins. We tested the model for thousands of different lac operator sequences with a protein binding microarray and by observing kinetics for individual lac repressor molecules in single-molecule experiments. We found that sequence specificity is mainly governed by the efficiency with which the protein recognizes different targets. The variation in probability of recognizing different targets is at least 1.7 times as large as the variation in microscopic dissociation rates. Modulating the rate of binding instead of the rate of dissociation effectively reduces the risk of the protein being retained on nontarget sequences while searching.
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