Cellular Toolkit for DNA Repair Found by Yale Researchers

Yale researchers have identified key mechanisms used to repair breaks in DNA strands, a fundamental question in biology with implications for cancer research.

Chromosomes are constantly under assault from environmental threats such as radiation and, as a consequence, suffer breaks in strands of DNA. If left unrepaired, these DNA breaks can lead to the development of cancer. The process of break repair is so complex it has baffled scientists for decades.

In a paper published in the September 2 issue of the journal Nature, the Yale team and collaborators at the Baylor School of Medicine identified 10 proteins crucial to the process and outlined how those proteins interact to initiate the repair of the breaks.

“It has taken the field 20 years to get to this point, and this paper paves the way for us to clarify the detailed mechanism of the break repair process and will surely keep us busy for many more years,” said Patrick Sung, chair of the department of molecular biophysics and biochemistry, researcher at the Yale Cancer Center and senior author of the paper. “This has tremendous relevance to cancer research, because when this pathway is not operational, cancer will arise.”

Several papers in the past two years have identified genes involved in chromosomal break repair and helped the Yale team pinpoint proteins involved. They were able to purify the proteins and study their individual roles in the repair process.

“We are now able to ask very detailed questions about these mechanisms,” Sung said.
The study opens up numerous avenues for cancer researchers. For instance, the BRCA2 and PALB2 mutations that confer a greater risk of breast and other cancers have been traced to defects in DNA break repair.

Other Yale authors on the paper are Hengyao Niu, Zhu Zhu, Youngho Kwon, Weixing Zhao,Peter Chi, Rohit Prakash, Changhyun Seong, Dongqing Liu, and Lucy Lu.

The work was funded by research grants from the National Institutes of Health and a postdoctoral fellowship from the Susan G. Komen for the Cure Foundation.