Potential Anti-cancer Drug has Novel Mechanism of Action

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

by Raven Hanna, SSRL Headlines

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

by Ziba Mahdavi

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

Events

Today (12:30 p.m.) Experimental Seminar: Progress, Results from the DRIFT Dark Matter Search

Access

Announcements

Lab Announcements

Community Bulletin Board

Status Update from KEK in Japan

Training

Lab Training

Calendar
Registration

Today (1:00 p.m.) Project Management II, Session One

Upcoming Workshops & Classes

Mar 29 (8:30 a.m.) Project Management II, Session Two

News

CERN Particle Collisions Resume Reuters
Physicists Take Stock of Quake Damage Physicsworld
African Astronomers Find New Use for Discarded Satellite Dishes Science Insider

<% Response.AddHeader "Last-modified", getArticleDate() 'Response.AddHeader "Last-modified","Mon, 01 Sep 1997 01:03:33 GMT" 'Monday, December 06, 2010 %>

View online at http://today.slac.stanford.edu/.

Potential Anti-cancer Drug has Novel Mechanism of Action RNA polymerase II stalled by a pyriplatin-DNA modification. (Image courtesy Dong Wang et al.) by Raven Hanna, SSRL Headlines 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 by Ziba Mahdavi 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	Events Today (12:30 p.m.) Experimental Seminar: Progress, Results from the DRIFT Dark Matter Search Access Bldg. 28 Renovation Driveway Access at Bldgs. 28, 26 RSB Project Info and Updates Announcements Lab Announcements RWT II, LCRA Training Now Online Malware Warning Software Spring Cleaning Community Bulletin Board Status Update from KEK in Japan Training Lab Training Calendar Registration Today (1:00 p.m.) Project Management II, Session One Upcoming Workshops & Classes Mar 29 (8:30 a.m.) Project Management II, Session Two News CERN Particle Collisions Resume Reuters Physicists Take Stock of Quake Damage Physicsworld African Astronomers Find New Use for Discarded Satellite Dishes Science Insider
	Flea Market Linear Café Menu Employee Milestones Search the Archives Subscribe non-SLAC e-mail Send Us Your Feedback

<% Response.AddHeader "Last-modified", getArticleDate() 'Response.AddHeader "Last-modified","Mon, 01 Sep 1997 01:03:33 GMT" 'Monday, December 06, 2010 %> View online at http://today.slac.stanford.edu/.


	Tuesday - March 15, 2011