Navigation Links
UC Davis researchers discover complexities of DNA repair
Date:10/23/2011

(SACRAMENTO, Calif.) An international team of scientists led by UC Davis researchers has discovered that DNA repair in cancer cells is not a one-way street as previously believed. Their findings show instead that recombination, an important DNA repair process, has a self-correcting mechanism that allows DNA to make a virtual u-turn and start over.

The study's findings, which appear in the Oct. 23 online issue of the journal Nature, not only contribute new understanding to the field of basic cancer biology, but also have important implications for potentially improving the efficacy of cancer treatments.

"What we discovered is that the DNA repair pathway called recombination is able to reverse itself," said Wolf-Dietrich Heyer, UC Davis professor of microbiology and of molecular and cellular biology and co-leader of Molecular Oncology at UC Davis Cancer Center. "That makes it a very robust process, allowing cancer cells to deal with DNA damage in many different ways. This repair mechanism may have something to do with why some cancer cells become resistant to radiation and chemotherapy treatments that work by inducing DNA damage."

Heyer likens this self-correcting ability of the DNA repair system to driving in a modern city where u-turns and two-way streets make it easy to rectify a wrong turn. "How much harder would it be to re-trace your path if you were in a medieval Italian city with only one-way streets," he said.

In the current study, Heyer and his colleagues used yeast as a model system to elucidate the mechanisms of DNA repair. They expect their findings, like most that come out of work on yeast, will be confirmed in humans. "Whether in yeast or humans, the pathways that repair DNA are the same," Heyer said.

The research team used electron microscopy to observe repair proteins in action on strands of DNA. They saw a presynaptic filament called Rad51 regulating the balance between one enzyme (Rad55-Rad57) that favors recombination repair and another (Srs2) that inhibits recombination repair. By controlling the balance between the two enzymes, Rad51 can initiate genetic repair - or the u-turn - as needed.

"It is a tug-of-war that has important implications for the cell because, if recombination occurs at the wrong time in the wrong place, the cell may die as a consequence." The ability of the repair system to abort ill-fated repair attempts, gives the cell a second shot, improving cellular survival after its DNA is damaged. This is exactly what is dreaded in cancer treatment.

"There are a lot of hints in the scientific literature suggesting that DNA repair contributes to resistance to treatments that are based on inducing DNA damage such as radiation or certain types of chemotherapy," Heyer said. "The ability of cancer cells to withstand DNA damage directly affects treatment outcome, and understanding the fundamental mechanisms of the DNA repair systems will enable new approaches to overcome treatment resistance."

Heyer said the team's next step is to look at the enzyme system in humans and see whether they find the same principles at work. This work has received funding and has already begun. One application of this work will be to target the self-correcting mechanism in cancer cells as a way of sensitizing them to radiation and/or chemotherapy treatments.

"If we can confirm that these types of mechanisms exist in human cells, then we will have an approach for making cancer cells more sensitive to DNA damage-inducing treatments."


'/>"/>

Contact: Dorsey Griffith
dorsey.griffith@ucdmc.ucdavis.edu
916-734-9118
University of California - Davis Health System
Source:Eurekalert

Related biology news :

1. UC Davis neurosurgeons use adult stem cells to grow neck vertebrae
2. UC Davis researchers find disease-causing fat cells in those with metabolic syndrome
3. 2 UC Davis plant biologists named as HHMI-GBMF investigators
4. NCI partners with Jackson Laboratory, UC Davis to speed cancer clinical trials
5. AAAS news briefs from UC Davis
6. UC Davis energy experts to help US Navy get greener
7. Death in the bat caves: UC Davis experts call for action against fast-moving disease
8. UC Davis study shows plants moved downhill, not up, in warming world
9. UC Davis study: Wild salmon decline was not caused by sea lice from farm salmon
10. UC Davis study links obesity with lowest earnings
11. At UC Davis, South Americans learn to help health, environment and industry back home
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/16/2016)... , June 16, 2016 ... is expected to reach USD 1.83 billion by ... View Research, Inc. Technological proliferation and increasing demand ... are expected to drive the market growth. ... The development of advanced multimodal techniques ...
(Date:6/9/2016)... 2016 Paris Police Prefecture ... security solution to ensure the safety of people and operations ... the major tournament Teleste, an international technology group ... announced today that its video security solution will be utilised ... up public safety across the country. The system roll-out is ...
(Date:6/2/2016)... LONDON , June 2, 2016 ... has awarded the 44 million US Dollar project, ... Security Embossed Vehicle Plates including Personalization, Enrolment, and IT Infrastructure ... world leader in the production and implementation of Identity Management ... in January, however Decatur was selected ...
Breaking Biology News(10 mins):
(Date:6/27/2016)... ... June 27, 2016 , ... ... medical technologies, services and solutions to the healthcare market. The company's primary focus ... distribution, manufacturing, sales and marketing strategies that are necessary to help companies efficiently ...
(Date:6/24/2016)... June 24, 2016  Regular discussions on a range of ... between the two entities said Poloz. Speaking at ... Ottawa , he pointed to the country,s inflation target, ... government. "In certain ... institutions have common economic goals, why not sit down and ...
(Date:6/23/2016)... ... June 23, 2016 , ... Mosio, a leader ... “Clinical Trials Patient Recruitment and Retention Tips.” Partnering with experienced clinical research professionals, ... providing practical tips, tools, and strategies for clinical researchers. , “The landscape of ...
(Date:6/23/2016)... SILVER SPRING, Md. , June 23, 2016 ... evidence collected from the crime scene to track the criminal ... sick, and the U.S. Food and Drug Administration (FDA) uses ... Sound far-fetched? It,s not. ... whole genome sequencing to support investigations of foodborne illnesses. Put ...
Breaking Biology Technology: