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First look at an enzyme target for antibacterial and cancer drugs
Date:12/20/2007

The veil has finally been lifted on an enzyme that is critical to the process of DNA transcription and replication, and is a prime target of antibacterial and anticancer drugs. Researchers with the U.S. Department of Energys Lawrence Berkeley National Laboratory (Berkeley Lab) and the University of California (UC) at Berkeley have produced the first three-dimensional structural images of a DNA-bound Type II topoisomerase (topo II) that is responsible for untangling coiled strands of the chromosome during cell division.

Preventing topo II from disentangling a cells DNA is fatal to the cell, which is why drugs that target topo II serve as agents against bacterial infections and some forms of cancer. This first ever structural image of topo II should help in the development of future antibacterial and anticancer drugs that are even more effective and carry fewer potential side effects.

Topo II has been called natures magician because it literally can move one DNA segment through another, said James Berger, a biochemist and structural biologist who led this research. The enzyme cleaves a double-stranded DNA, passes a second duplex through the break, and then immediately repairs the broken strands. This enables topo II to control the topology of DNA for chromosome segregation and disentanglement.

Berger holds a joint appointment with Berkeley Labs Physical Biosciences Division, and UC Berkeleys Department of Molecular and Cell Biology. He and Ken Dong, a graduate student in his research group, co-authored a paper reporting this research in the December 20, 2007 issue of the journal Nature. The paper is titled: Structural basis for Gate-DNA recognition and bending by type IIA topoisomerases.

Using the exceptionally bright and intense beams of x-rays generated at Berkeley Labs Advanced Light Source (ALS), Berger and Dong obtained high resolution, 3-D crystallography images of the DNA binding and cleavage core of a topo II enzym
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Contact: Lynn Yarris
lcyarris@lbl.gov
510-486-5375
DOE/Lawrence Berkeley National Laboratory  
Source:Eurekalert

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First look at an enzyme target for antibacterial and cancer drugs
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