Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Oncologists could gain therapeutic advantage by targeting telomere protein

20.02.2006


Inactivating a protein called mammalian Rad9 could make cancer cells easier to kill with ionizing radiation, according to research at Washington University School of Medicine in St. Louis.



The researchers found that Rad9, previously considered a "watchman" that checks for DNA damage, is actually a "repairman" that fixes dangerous breaks in the DNA double helix. They found Rad9 is especially active in telomeres, the protective ends of chromosomes.

Because of this new role, Rad9 has gained the researchers’ interest as a potential target for cancer therapy -- knocking out Rad9 would enhance the power of radiation treatments by making it easier for radiation to inflict fatal damage to a tumor’s genetic material. Their study appears in the March issue of the journal Molecular and Cellular Biology, which is now available online.


"Our study suggests that if we could inactivate Rad9 in tumor cells, we would be able to kill them with a very low dose of radiation and gain a therapeutic advantage," says senior author Tej K. Pandita, Ph.D., associate professor of radiation oncology and on the faculty of the Siteman Cancer Center at Washington University School of Medicine and Barnes-Jewish Hospital.

The study revealed that Rad9 proteins interact with chromosomes’ telomeres, which are special structures at the ends of chromosomes that protect them from fusion or degradation. Specifically, Rad9 proteins were shown to interact with proteins called telomere binding proteins. When the scientists inactivated Rad9 in human cells, they saw damage to chromosomes and end-to-end fusion at telomeres. DNA damage and chromosomal fusion can disrupt the cell cycle and cause cell death. Because radiation treatments increase these incidents, loss of Rad9 in cancer cells could enhance the killing effect of radiation.

Previous research had suggested that Rad9 maintains cell cycle checkpoint controls--scientists thought that the protein helped monitor DNA during replication and signaled the cell to stop its growth cycle if damage was detected. That role is not supported by this current research, and it has become evident that Rad9 directs the repair of DNA damage instead, according to Pandita,.

"We saw that Rad9 stabilizes telomeres, and because we aren’t yet sure how it does it, we will continue to study how Rad9 influences the telomere structure," Pandita says. "We speculate that without Rad9, some of the other proteins associated with the telomeric structure become delocalized, exposing the DNA at the ends of chromosomes."

In addition to being able to enhance radiosensitization of cancerous tissues by inactivating Rad9, the researchers would like to be able to identify people with mutations in Rad9 because such mutations could predispose a person to cancer.

"If Rad9 isn’t functioning properly in cells, it can lead to genomic instability and result in the malignant transformation of cells," Pandita says. "In fact, fusions at the telomeric ends of chromosomes like those seen in the absence of Rad9 appear frequently in tumor tissues."

The study’s findings place Rad9 at an important juncture: its function is vital to the health of cells, and this makes it a key vulnerability to exploit for cancer therapy.

Gwen Ericson | EurekAlert!
Further information:
http://www.wustl.edu

More articles from Life Sciences:

nachricht Atomic Design by Water
23.02.2018 | Max-Planck-Institut für Eisenforschung GmbH

nachricht Stiffness matters
22.02.2018 | Albert-Ludwigs-Universität Freiburg im Breisgau

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Developing reliable quantum computers

International research team makes important step on the path to solving certification problems

Quantum computers may one day solve algorithmic problems which even the biggest supercomputers today can’t manage. But how do you test a quantum computer to...

Im Focus: In best circles: First integrated circuit from self-assembled polymer

For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.

In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...

Im Focus: Demonstration of a single molecule piezoelectric effect

Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale

Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...

Im Focus: Hybrid optics bring color imaging using ultrathin metalenses into focus

For photographers and scientists, lenses are lifesavers. They reflect and refract light, making possible the imaging systems that drive discovery through the microscope and preserve history through cameras.

But today's glass-based lenses are bulky and resist miniaturization. Next-generation technologies, such as ultrathin cameras or tiny microscopes, require...

Im Focus: Stem cell divisions in the adult brain seen for the first time

Scientists from the University of Zurich have succeeded for the first time in tracking individual stem cells and their neuronal progeny over months within the intact adult brain. This study sheds light on how new neurons are produced throughout life.

The generation of new nerve cells was once thought to taper off at the end of embryonic development. However, recent research has shown that the adult brain...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on High Temperature Shape Memory Alloys (HTSMAs)

15.02.2018 | Event News

Aachen DC Grid Summit 2018

13.02.2018 | Event News

How Global Climate Policy Can Learn from the Energy Transition

12.02.2018 | Event News

 
Latest News

Stiffness matters

22.02.2018 | Life Sciences

Magnetic field traces gas and dust swirling around supermassive black hole

22.02.2018 | Physics and Astronomy

First evidence of surprising ocean warming around Galápagos corals

22.02.2018 | Earth Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>