Scientists Uncover Secrets of Potent DNA Toxin

One of the most potent of known toxins acts by joining the two strands of the DNA double helix together in a unique fashion which foils the standard repair mechanisms cells use to protect their DNA. A team of Vanderbilt University researchers has worked out the molecular details that explain how this bacterial toxin -- yatakemycin (YTM) -- prevents DNA replication. The team’s results, described in a paper published online on July 24, 2017 in Nature Chemical Biology, explain YTM's extraordinary toxicity and could be used to fine-tune the compound's impressive antimicrobial and antifungal properties. The article is titled “Toxicity and Repair of DNA Adducts Produced by the Natural Product Yatakemycin.” YTM is produced by some members of the Streptomyces family of soil bacteria to kill competing strains of bacteria. It belongs to a class of bacterial compounds that are currently being tested for cancer chemotherapy because their toxicity is extremely effective against tumor cells. "In the past, we have thought about DNA repair in terms of protecting DNA against different kinds of chemical insults," said Professor of Biological Sciences Brandt Eichman. "Now, toxins like YTM are forcing us to consider their role as part of the ongoing chemical warfare that exists among bacteria, which can have important side effects on human health." Cells have developed several basic types of DNA repair, including base excision repair (BER) and nucleotide excision repair (NER). BER generally fixes small lesions and NER removes large, bulky lesions. A number of DNA toxins create bulky lesions that destabilize the double helix.
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