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:5/24/2017)... ... 24, 2017 , ... Myers Jackson is well known for auctioning homes that ... homes anywhere on the planet. The luxury home market is alive and well and ... A quick search of “11 Spyglass Hill Auction will enlighten you on the dynamics ...
(Date:5/24/2017)... ... May 24, 2017 , ... Medic CE , a Career Step company, ... Septic Shock” hosted by the Journal of Emergency Medical Services (JEMS). The free webinar, ... be presented by Captain Rommie Duckworth, LP, a career fire captain as well as ...
(Date:5/24/2017)... ... May 24, 2017 , ... Adelberg-Montalvan ... dentistry options for its patients on Long Island, New York. , Holistic ... being, and is one of the biggest trends in dentistry today. , ...
(Date:5/24/2017)... ... 24, 2017 , ... Fiberstar, Inc., http://www.FiberstarIngredients.com a ... beverage industry offers Citri-Fi®, a natural citrus fiber, to improve beverage ingredient declarations. ... a result, labels need to deliver simple, transparent and clear messaging. Listed food ...
(Date:5/23/2017)... ... May 23, 2017 , ... ... Clinical Integration company, announced today that its iClinic V12.2 solution has achieved approval ... NCQA recently introduced PCMH 2017 standards which emphasize team-based care with a ...
Breaking Medicine News(10 mins):
(Date:5/10/2017)... , May 10, 2017 Global Health Intelligence ... Latin America , published its 2017 ranking of ... is based on extensive data analysis from GHI,s hospitals ... hospitals database for the region. The GHI database covers 86% ... offering more than 130 data points for each institution in ...
(Date:5/9/2017)... 2017 Zimmer Biomet Holdings, Inc. (NYSE and ... announced it has earned a spot on Forbes, ... Company was ranked among 500 U.S. employers as well ... Equipment and Services. The annual Forbes ... independent survey of over 30,000 employees across 25 industries. ...
(Date:5/8/2017)... , May 8, 2017 MACRA replaces ... from fee for service reimbursement. Black Book Research crowdsource-surveyed ... 1.       The Market for MIPS Compliance Technology ... of physician practices with 3 or more clinicians seek ... by Q4. "Given the magnitude of the changes, the ...
Breaking Medicine Technology: