SLAC Today is available online at:

In this issue:
Potential Anti-cancer Drug has Novel Mechanism of Action
Japan Earthquake and Tsunami Relief Bake Sale Monday

SLAC Today

Tuesday - March 15, 2011

Potential Anti-cancer Drug has Novel Mechanism of Action

RNA polymerase II stalled by a pyriplatin-DNA modification. (Image courtesy Dong Wang et al.)

Cisplatin, a platinum-based anti-cancer drug, is a widely used and effective cancer chemotherapy drug. It slows the growth of cancer cells through DNA modification, creating chemical links that serve as a roadblock when the cancer cell attempts to transcribe the DNA into RNA. Since cancer cells can develop resistance to cisplatin and related drugs, researchers are interested in finding alternative treatments with different targets or mechanisms of action. Pyriplatin, one member of a potentially larger class of candidates, shows promise because it remains active in cisplatin-resistant cells and has different chemical and biological properties. Whereas most chemically modified DNA affects transcription at the site where it is altered, DNA modified by pyriplatin can be transcribed along its length through the altered base, but cannot continue farther.

A team of researchers led by Stephen Lippard of MIT and Dong Wang of UC San Diego used macromolecular crystallography Beamline 11-1 at the Stanford Synchrotron Radiation Lightsource to solve crystal structures of molecules performing transcription that was stalled by pyriplatin modification. They found that structural changes in the DNA allow the pyriplatin-modified site to be transcribed but prevent the next DNA base from swinging into the active site of the molecule performing transcription, DNA polymerase. Pyriplatin thus has a transcription-stalling mechanism that is significantly different from that achieved by cisplatin.

The mechanism revealed by this study will allow further development of different and more potent anti-cancer drugs. This work was published in the May 25, 2010 issue of the Proceedings of the National Academy of Sciences.

To learn more about this research see the full scientific highlight.

Japan Earthquake and Tsunami Relief Bake Sale Monday

Next Monday, March 21, from 8:30 to 9:30 a.m. and from 11:30 to 2:30 p.m. on the Kavli patio (west side entrance), you can buy a homemade breakfast or sweet treat and contribute to relief for the victims of Friday's earthquake and tsunami in Japan. Check or cash donations are also welcome, and tax deductible. The proceeds from the bake sale and your donations will be given to the International American Red Cross Japan Relief Funds.

Please contact Ziba Mahdavi (x2846) if you would like to help or have questions




 Lab Announcements

Community Bulletin Board


Lab Training

Upcoming Workshops & Classes


dividing line
(Office of Science/U.S. DOE Logo)

View online at