How Not to Make Sausages: The Role of Thermus thermophilus Argonaute In Vivo
Dr. Zamore is professor and chair of the RNA Therapeutics Institute at the University of Massachusetts Medical School and an investigator with the Howard Hughes Medical Institute. He specializes in the study of argonautes, the only known family of proteins that can be programmed with any RNA or DNA sequence to make sequence-specific regulators of transcription, mRNA stability, or translation.
Animals, plants, and other eukaryotes use Argonaute proteins, guided by short RNA sequences, to defend cells against transposons and viruses. Many bacterial genomes also encode Argonaute proteins, but their functions remain unknown. The best studied eubacterial Argonaute is the DNA-guided protein TtAgo from Thermus thermophilus. TtAgo has been proposed to defend T. thermophilus against transformation by DNA plasmids, a function analogous to transposon defense in eukaryotes. I will describe our discovery that in T. thermophilus, TtAgo confers resistance to the antibiotic ciprofloxacin. Ciprofloxacin blocks bacterial growth by inhibiting the enzyme gyrase, which separates the topologically linked chromosomes that result from replicating circular DNA. TtAgo provides an alternative route to chromosome decatenation in the absence of functional gyrase, allowing the bacterium to finish replicating its circular genome. The mechanism of TtAgo DNA guide acquisition and the in vivo function of TtAgo will be presented.
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