Navigation Links
Some cells don't know when to stop
Date:11/19/2012

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.


'/>"/>

Contact: Robert Perkins
perkinsr@usc.edu
213-740-9226
University of Southern California
Source:Eurekalert

Related medicine news :

1. New drug prevents spread of human prostate cancer cells
2. Tiny hitchhikers attack cancer cells
3. To prevent leukemias dreaded return, go for the stem cells
4. Scientists identify major source of cells defense against oxidative stress
5. Therapy exploits addiction of leukemia cells
6. IBN discovers human neural stem cells with tumor targeting ability
7. Leukaemia cells have a remembrance of things past
8. Small molecular bodyguards kill HPV-infected cancer cells by protecting tumor-suppressor
9. Research yields new clues to how brain cancer cells migrate and invade
10. Presence of fetal cells in women lowers risk of breast cancer but raises risk of colon cancer
11. Researchers Rejuvenate Blood-Forming Stem Cells in Mice
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/26/2016)... , ... June 26, 2016 , ... Pixel Film Studios ... X. , "Film editors can give their videos a whole new perspective by using ... - CEO of Pixel Film Studios. , ProSlice Levels contains over 30 Different ...
(Date:6/25/2016)... ... June 25, 2016 , ... Austin residents seeking Mohs surgery services, can ... Surgery and to Dr. Russell Peckham for medical and surgical dermatology. , Dr. Dorsey ... cancer. The selective fellowship in Mohs Micrographic Surgery completed by Dr. Dorsey was under ...
(Date:6/25/2016)... ... June 25, 2016 , ... Dr. Calvin Johnson has dedicated ... has implemented orthobiologic procedures as a method for treating his patients. The procedure ... doctors to perform the treatment. Orthobiologics are substances that orthopaedic surgeons use to ...
(Date:6/24/2016)... ... 2016 , ... June 19, 2016 is World Sickle Cell Observance Day. In ... benefits of holistic treatments, Serenity Recovery Center of Marne, Michigan, has issued ... Sickle Cell Disease (SCD) is a disorder of the red blood cells, which can ...
(Date:6/24/2016)... , ... June 24, 2016 , ... Comfort Keepers® of ... Cancer Society and the Road To Recovery® program to drive cancer patients to and ... other adults to ensure the highest quality of life and ongoing independence. Getting ...
Breaking Medicine News(10 mins):
(Date:6/26/2016)... 2016 Jazz Pharmaceuticals plc (Nasdaq: ... Hart-Scott-Rodino Antitrust Improvements Act of 1976, as amended ("HSR"), ... Inc. ("Celator"; Nasdaq: CPXX ) expired effective ... As previously announced on May 31, 2016, ... agreement under which Jazz Pharmaceuticals has commenced a tender ...
(Date:6/24/2016)... Calif. , June 24, 2016  Global ... a biopharmaceutical company developing novel therapeutics for the ... needs, today announced the closing of its previously ... common stock, at the public offering price of ... the offering were offered by GBT. GBT estimates ...
(Date:6/24/2016)... 24, 2016 Dehaier Medical Systems Ltd. (NASDAQ: ... develops, markets and sells medical devices and wearable sleep ... a strategic cooperation agreement with Hongyuan Supply Chain Management ... on June 20, 2016, to develop Dehaier,s new Internet ... agreement, Dehaier will leverage Hongyuan Supply Chain,s sales platform ...
Breaking Medicine Technology: