In times of stress and genetic damage, some DNA repair enzymes can relocate to the part of the cell that needs their help, according to a collaborative team study led by scientists at Emory University School of Medicine.
The study found that the signal that prompts relocation is oxidative stress-an imbalance of cellular metabolism connected with several human diseases.
AdvertisementDr. Paul Doetsch, professor of Biochemistry, Radiation Oncology, and Hematology and Oncology, says that the finding may lead to new targets for anti-cancer drugs that interfere with DNA repair.
"DNA damage and oxidative stress are very closely related. For example, the way radiation inflicts most of its damage on DNA is through oxidative stress. The more we know about how cells respond to oxidative stress, the more chances there could be to influence those responses for diagnostic or therapeutic purposes," said Doetsch.
The DNA inside cells already remains under assault by heat, radiation, and oxygen.
And cells have an extensive set of repair enzymes that comb through DNA, continually excising and re-copying damaged segments. Also, mitochondria (cells' miniature power plants) have their own DNA.
For the study, the researchers genetically modified strains of yeast so that two different DNA repair enzymes would be fluorescent.
They could track the enzymes around the cell when yeast was exposed to hydrogen peroxide, causing oxidative stress, or to other chemicals causing DNA damage.
It was found that one DNA repair enzyme they studied, Ntg1, moves to the nucleus or the mitochondria depending on where DNA damage is concentrated.
On the other hand, a related enzyme, Ntg2, remains in the nucleus under all conditions.
The authors found that the cells apparently direct Ntg1's relocation by briefly attaching a small protein called SUMO to what needs to be moved around.
SUMO is found in fungi, plants and animals and is already being investigated by several research groups as a possible target for anti-cancer drugs.
The study has been published in the journal Molecular and Cellular Biology.