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Peering at a machine that pries DNA apart

X-ray crystallography gives scientists new understanding of molecular motor

Boston, MA--October 12, 1999--Harvard researchers have created the first atomic-resolution image of a donut-shaped enzyme, or helicase, that unwinds the DNA double helix to expose its genetic letters for DNA replication. Michael Sawaya, postdoctoral fellow in the lab of Tom Ellenberger, associate professor of biological chemistry and molecular pharmacology (BCMP), worked out the X-ray crystallographic structure reported in the October 15 Cell. The structure is rendered in pictures that show how six individual polypeptide lobes arrange themselves in space to look a bit like a ring of bread buns. It affords researchers the first detailed glance at a family of proteins that remain enigmatic in spite of their recognized status as a fundamental molecular machine of the cell.

"We know next to nothing about how these helicases move on DNA," says Ellenberger. Helicases have become a competitive field of inquiry because defects in human forms underlie several diseases, including the cancer-prone Bloom's syndrome and a disease of premature aging called Werner syndrome. Helicases are interesting for several reasons. First, they are molecular motors, just like myosin, which moves along actin fibrils to contract a muscle, or kinesin, which transports cargo along microtubules. The ring-shaped kind of helicase threads one strand of DNA through its central hole and zips along the double strand at breakneck speed, ploughing through 300 paired nucleotides per second while shoving the second strand out of the way. The enzyme is powerful, too. Other researchers have placed "roadblocks" in the helicase's way by binding proteins on the DNA's back. Yet the helicase knocked these off as it forced its way through.

Second, helicases came in different shapes--some are monomers, others dimers--and they do all sorts of things. The ring-shaped, hexameric helicase studied here spearhea
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Contact: Peta Gillyatt
gillyatt@hms.harvard.edu
617-432-0443
Harvard Medical School
15-Oct-1999


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