Virus researchers close in on the secret life of DNA

Z-DNA, a long-known but still mysterious alternate configuration of DNA, is involved in cellular defenses against viral attack according to the results of a series of experiments linking Z-DNA binding proteins with lethality in pox viruses.

The research appears may point towards important answers to the unsolved puzzle of how this alternate form of DNA functions and may lead to the development of anti-viral compounds that are effective against smallpox, one of the deadliest of human diseases. A report on the research by two teams of scientists from the Massachusetts Institute of Technology and Arizona State University is forthcoming in the May 19 Online Early Edition of the Publication of the National Academy of Sciences. Entitled "A role for Z-DNA binding in vaccinia virus athogenesis," the paper is authored by Yang-Gyun Kim, Ky Lowenhaupt, and Alexander Rich from MIT and Maneesha Muralinath, Teresa Brandt, Matthew Pearcy, Kevin Hauns and Bertram L. Jacobs from ASU. Z-DNA, discovered by MIT's Rich in 1979, is an alternate zig-zig-shaped form (or "conformation") that DNA sometimes assumes instead of the familiar double helix conformation (known as B-DNA). Certain sequences of DNA in the normal B conformation will "flip" into the Z form (which is less stable), apparently in response to genes being transcribed immediately "downstream" on the molecule's sequence. Coiled to the left instead of to the right, the Z-DNA conformation is a significantly different arrangement of the molecule, but the functional role of this major difference has remained largely unclear.

In the report, the researchers find clear evidence that a critical pox virus protein (one known to be necessary for the virus to disable animal cell defenses) works by binding to Z-DNA and apparently interfering in its operation.

The researchers aimed a variety of experiments towards understanding the functionality of vaccinia virus protein E3L, a protein previous experiments h

Contact: James Hathaway
Arizona State University

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