Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Some cells don't know when to stop

20.11.2012
Certain mutated cells keep trying to replicate their DNA — with disastrous results — even after medications rob them of the raw materials to do so, according to new research from USC.

New imaging techniques allowed scientists to see for the first time that while chemotherapy drugs shut down the DNA replication process of most cancer cells, so-called "checkpoint mutants" just keep chugging along, unwinding the DNA and creating damaged DNA strands that can result in the kind of abnormalities seen in cancer cells.

"Older methods suggested that these checkpoint mutants stopped replicating and that the replication machinery simply fell apart to cause DNA damage," said Susan Forsburg, professor of molecular biology at the USC Dornsife College of Letters, Arts and Sciences. "Our new technique suggests that replication processes continue and actively contribute to the damage."

Forsburg is the corresponding author on a paper about the discovery that was published online in Molecular & Cellular Biology in October. She collaborated with lead author Sarah Sabatinos, a postdoctoral research associate at USC, and Marc Green, a research technician.

The team used a common chemotherapy drug to put stress on fission yeast cells while they were going through the DNA replication process. The drug starves cells for nucleotides, which are the molecules that cells use to build DNA strands.

Previous studies showed that normal cells recognize the loss of nucleotides and stop trying to replicate their DNA — similar to how a driver who runs low on gas stops before he runs the engine dry.

What the researchers found is that the checkpoint mutants ignore this signal. Using the metaphor above, the driver of the car can't take his foot off of the accelerator and keeps going until his engine sputters to a stop. While this won't necessarily damage a car engine, it's catastrophic for DNA.

These mutant cells keep trying to replicate their DNA, unwinding the strands, until the DNA strands reach a "collapse point" where they break — arguably the worst kind of damage that can be done to a cell.

"We predict that this is a source of increased cancer risk in human cells that harbor checkpoint mutations," Sabatinos said. "Replication-fork instability or collapse may occur at a low frequency in these mutated cells without drug treatment, leading to more frequent DNA changes down the road."

The next step will be to determine what happens to the small fraction of mutant cells that survive this treatment.

"By bringing to bear a sophisticated combination of genetic tools, drug treatment and state-of-the-art imaging, Susan Forsburg and her co-workers have elicited a fresh perspective on a long-standing problem," said Michael Reddy, who oversees DNA replication grants at the National Institutes of Health's National Institute of General Medical Sciences, which funded the work.

"Their fundamentally revised scenario of the dynamics of fork collapse is likely to lead to invaluable insights as to how checkpoint-defective human cancer cells preserve their DNA, thereby resisting chemotherapy," he said.

A time-lapse video of cells, imaged to display a single strand of DNA (light blue) and DNA breaks (yellow) during drug treatment, can be found online here: http://youtu.be/preMPZjPWgQ

Robert Perkins | EurekAlert!
Further information:
http://www.usc.edu
http://youtu.be/preMPZjPWgQ

More articles from Life Sciences:

nachricht Topologische Quantenchemie
21.07.2017 | Max-Planck-Institut für Chemische Physik fester Stoffe

nachricht Topological Quantum Chemistry
21.07.2017 | Max-Planck-Institut für Chemische Physik fester Stoffe

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Manipulating Electron Spins Without Loss of Information

Physicists have developed a new technique that uses electrical voltages to control the electron spin on a chip. The newly-developed method provides protection from spin decay, meaning that the contained information can be maintained and transmitted over comparatively large distances, as has been demonstrated by a team from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute. The results have been published in Physical Review X.

For several years, researchers have been trying to use the spin of an electron to store and transmit information. The spin of each electron is always coupled...

Im Focus: The proton precisely weighted

What is the mass of a proton? Scientists from Germany and Japan successfully did an important step towards the most exact knowledge of this fundamental constant. By means of precision measurements on a single proton, they could improve the precision by a factor of three and also correct the existing value.

To determine the mass of a single proton still more accurate – a group of physicists led by Klaus Blaum and Sven Sturm of the Max Planck Institute for Nuclear...

Im Focus: On the way to a biological alternative

A bacterial enzyme enables reactions that open up alternatives to key industrial chemical processes

The research team of Prof. Dr. Oliver Einsle at the University of Freiburg's Institute of Biochemistry has long been exploring the functioning of nitrogenase....

Im Focus: The 1 trillion tonne iceberg

Larsen C Ice Shelf rift finally breaks through

A one trillion tonne iceberg - one of the biggest ever recorded -- has calved away from the Larsen C Ice Shelf in Antarctica, after a rift in the ice,...

Im Focus: Laser-cooled ions contribute to better understanding of friction

Physics supports biology: Researchers from PTB have developed a model system to investigate friction phenomena with atomic precision

Friction: what you want from car brakes, otherwise rather a nuisance. In any case, it is useful to know as precisely as possible how friction phenomena arise –...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Closing the Sustainability Circle: Protection of Food with Biobased Materials

21.07.2017 | Event News

»We are bringing Additive Manufacturing to SMEs«

19.07.2017 | Event News

The technology with a feel for feelings

12.07.2017 | Event News

 
Latest News

NASA looks to solar eclipse to help understand Earth's energy system

21.07.2017 | Earth Sciences

Stanford researchers develop a new type of soft, growing robot

21.07.2017 | Power and Electrical Engineering

Vortex photons from electrons in circular motion

21.07.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>