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We seek to understand the biochemical and biophysical principles by which DNA is repaired, starting with relatively simple repair pathways such as BER. For all DNA repair pathways we are interested in specificity (distinguishing damaged and normal DNA) and fidelity (how efficiently the damage is repaired). The physical principles and mechanisms by which specificity and fidelity are conferred are best addressed by mechanistic analysis in vitro. Ultimately, the chemical and physical principles governing the action of BER enzymes will be more broadly applicable to other DNA repair processes, and to other DNA-templated activities such as replication. For example, the processes of locating rare sites and coordinating multi-step, multi-component pathways have features common to most DNA-templated activities. By focusing on the human proteins we hope to speed the process by which mechanistic insight leads to practical applications, such as the improvement of anticancer chemotherapies, protection from environmental carcinogens, and the development of novel antimicrobials.
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Nature structural & molecular biologyno. 8 (2023): 1077-1091
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