Archaeal DNA Repair

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Archaea often thrive in extreme environments that accelerate DNA damage. There is a lack of comprehensive understanding of the molecular features that impart extreme resistance to DNA damage exhibited by many Archaea. This project aims to resolve the processes that maintain, replicate and repair the genome of the model archaeon Thermococcus kodakarensis. The focus is on elucidating unknown fitness benefits, specificities, rates and mechanisms underlying many archaeal DNA repair pathways. The outcomes will help clarify how DNA lesions are recognized and repaired, and how replication proceeds on lesion-containing DNAs in archaea and other organisms. The project provides research training and career development opportunities for students at all levels, including undergraduate and high school students, notably with immersive research experiences in academic, private and federal laboratories. The project will employ a scaled approach, from purified enzyme kinetics in vitro to whole cell phenotypic assays and growth measurements. Novel, high-throughput assays will be used to probe mechanisms of archaeal DNA repair, discover new repair factors and establish the contributions of different DNA polymerases to DNA repair. Examination of multiple DNA repair and replicative pathways by complementary experimental techniques will yield a comprehensive mechanistic view of archaeal DNA repair and how the pathways collectively impart fitness to these organisms in extreme environments.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.