DNA splicing enzyme observed in action

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Molecule encircles DNA while connecting genetic fragments

Researchers in the lab of Tom Ellenberger, the Hsien Wu and Daisy Yen Wu professor of biological chemistry and molecular pharmacology at Harvard Medical School, reported the doughnut shape of human ligase I in the Nov. 25, 2004 issue of Nature. The details revealed by the ringlike structure suggest new ideas about the functions of this enzymatic workhorse and its two specialized cousins, ligases III and IV. These tend to occasional repairs of chromosomes dinged by life’s damaging exposures. Much of science begins with the simplest organisms and works its way up to investigate the more complicated and specialized analogues in humans. This time, the complexity of the human ligase made for a more stable molecular complex with DNA than do simpler viral ligases, which turned out to be necessary for the final crystal structure, said postdoc John Pascal, first author of the paper. Ligases do their jobs in nanoseconds, with no time to stop and pose for a curious biologist. Pascal’s biggest challenge was tinkering with the protein machinery and creating a condition in which the ligase would stall after it found disconnected DNA strands.