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A visit to the gas station: Protein helps power up DNA repair

Date:
December 3, 2015
Source:
UC Davis Comprehensive Cancer Center
Summary:
In a game-changing study, researchers have shown that the enzyme cyclin-dependent kinase 1 (CDK1), which plays a key role in DNA repair, also leaves the nucleus to boost cellular energy production. By irradiating normal cells, the team showed that CDK1 turned up production of ATP, cellular energy packets that -- in this case -- provided the necessary power supply to fix the radiation-damaged DNA.
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In a game-changing study, researchers at UC Davis and other organizations have shown that the enzyme cyclin-dependent kinase 1 (CDK1), which plays a key role in DNA repair, also leaves the nucleus to boost cellular energy production. By irradiating normal cells, the team showed that CDK1 turned up production of ATP, cellular energy packets that -- in this case -- provided the necessary power supply to fix the radiation-damaged DNA.

These findings could spur development of new therapies to protect healthy cells from radiation damage or sensitize cancer cells to radiation or chemotherapy. The study was published online today in the journal Cell Reports.

"We show, for the first time, that after radiation, mitochondrial ATP is required for DNA repair," said lead author Jian-Jian Li, professor and director of translational research in the UC Davis Department of Radiation Oncology. "Cells need to tell mitochondria to produce more energy or the cell may die. CDK1 sends this message from the nucleus to mitochondria to get that energy."

Cells have a built-in defense mechanism that repairs DNA damage. However, no one knew how they powered this operation. These new findings highlight a dual role for CDK1: providing essential DNA repairs while also requesting the energy needed to conduct those repairs.

This process is also interesting from an evolutionary standpoint, as mitochondria -- which were once unique organisms co-opted by cells eons ago -- have their own DNA. Over time, cells have learned to overcome the differences between nuclear and mitochondrial DNA to communicate effectively.

In the study, the team irradiated normal human breast and skin cells, as well as mouse skin cells, and then monitored CDK1 activity. They found that the protein quickly moved from the nucleus to mitochondria, scaling up energy production and DNA repair. When CDK1 was blocked, this process was severely restricted, with bad consequences for cells.

"If we cut the gas line," said Li, "the DNA repair is much less efficient, the DNA does not get repaired, and the cell dies."

This work provides key insights into an important cellular mechanism and could ultimately benefit cancer patients. For example, the DNA repair process could be boosted to protect normal cells in patients receiving radiation therapy.

But this new understanding of cellular mechanics could also show how tumor cells resist radiation treatments. In fact, the next step for Li will be to test this mechanism in cancer cells.

"How do tumor cells survive after high-dose radiation?" asks Li. "They must have very strong energy production to fix that damage."

Other researchers included: Lili Qin, Ming Fan, Demet Candas, Guochun Jiang, Stelios Papadopoulos and Lin Tian at UC Davis; Gayle Woloschak at Northwestern University; and David J. Grdina at the University of Chicago.

This research was funded, in part, by the National Institutes of Health (CA152313) and the Department of Energy Office of Science (DE-SC0001271).


Story Source:

Materials provided by UC Davis Comprehensive Cancer Center. Note: Content may be edited for style and length.


Cite This Page:

UC Davis Comprehensive Cancer Center. "A visit to the gas station: Protein helps power up DNA repair." ScienceDaily. ScienceDaily, 3 December 2015. <www.sciencedaily.com/releases/2015/12/151203142543.htm>.
UC Davis Comprehensive Cancer Center. (2015, December 3). A visit to the gas station: Protein helps power up DNA repair. ScienceDaily. Retrieved March 28, 2024 from www.sciencedaily.com/releases/2015/12/151203142543.htm
UC Davis Comprehensive Cancer Center. "A visit to the gas station: Protein helps power up DNA repair." ScienceDaily. www.sciencedaily.com/releases/2015/12/151203142543.htm (accessed March 28, 2024).

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