A biochemical analysis study has discovered a new role for the DNA2 enzyme.
The research, which was completed in the lab of Patrick Sung, professor of molecular biophysics and biochemistry at the Yale School of Medicine, looked at the way in which DNA2 repairs breaks in DNA that lead to the abnormalities that cause cancer. The researchers found that DNA2 will detect and cut DNA double-strand breaks — a discovery that helps clarify the mechanism behind DNA break repair.
“As human DNA2 is overexpressed in many tumors, it is a potential cancer therapeutic target,” said Xiaoyu Xue, an author on the paper and associate research scientist in the Molecular Biophysics and Biochemistry Department.
Breaks in DNA can cause rearrangements in chromosomes, according to the study, allowing for the formation of abnormalities and potentially leading to cancer.
Using yeast cells, the study found that when traveling down a single-stranded section of a DNA tail, DNA2 will cut the damaged DNA if it reaches a double-stranded region. This is an important step early in the repair process, according to the research.
Sung stressed the importance of studying the process of fixing these breaks, especially when they are induced by harmful chemicals or radiation.
“DNA double-strand breaks, or DSBs, can cause genome instability and cancer formation,” Xue said. “Thus they need to be repaired accurately. … [The] DNA2 protein plays an important role in the early steps of the DNA DSB repair pathway.”
The most exciting discovery from this research, according to Xue, is that DNA2 exhibits endonuclease activity differently when in the presence of the ATP molecule, meaning that the helicase activity of the molecule is important for long-range resection.
Xue added that the research indicated a possible inhibitor design against DNA2, either by inhibiting the helicase or the nuclease activity of the molecule.
“Our findings provide the experimental tools and experimental framework to further dissect the mechanism of DNA break repair and its impact on cancer avoidance,” Sung said. “It may constitute the basis for finding strategies to treat breast, ovarian and other cancers.”
According to statistics from the National Cancer Institute, 1,685,210 new cases of cancer were diagnosed during 2016.