Campus Connection

Wrench in the machinery
(continued)

Heyer, educated in Germany and Switzerland, has played a major role in the rapidly developing field. He has focused his research on DNA repair in yeast, painstakingly identifying the individual genes that are the nuts and bolts of the organism’s repair machinery, then figuring out the jobs each one does. Because yeast and human repair genes are so similar, despite the billion years of evolutionary distance that separate them, knowledge gained in yeast experiments can be applied directly to humans.

Of all the repair genes Heyer has studied, two have especially captured his interest: Rad54 and Rad51. The two genes act as a team to repair double-strand DNA breaks, one of the most complicated types of DNA damage to fix. In a double-strand break, both of the parallel strands of the DNA double helix are fractured.
Since 1997, Heyer has published 20 scientific papers on the two repair genes, becoming a leading authority on Rad54 and Rad51. Normal yeast with healthy versions of the two repair genes can survive up to 50 double-strand DNA breaks. But if either repair gene gets damaged, the yeast can’t handle even a single double-strand break.

Double-strand DNA breaks are the precise type of damage cells suffer when they are exposed to the radiation used in cancer treatment. Some chemotherapy drugs also cause double-strand DNA breaks. If Heyer can figure out a way to inhibit either or both of these repair genes in cancer cells, fewer of the malignant cells will be able to overcome the effects of radiation and chemotherapy. The cancers will be easier to destroy.

Rad54 and Rad51 represent just two potential targets, as cells have multiple ways to repair DNA damage. Blocking any of the key steps in DNA repair should also leave cancer cells more vulnerable. Indeed, Heyer says it may be necessary to inhibit multiple steps and multiple pathways at the same time.

“Looking for ways to inhibit DNA repair in cancer cells will be a growing part of our lab,” Heyer says. The ultimate goal will be a pharmaceutical agent capable of shutting down DNA repair in cancer cells, without impairing DNA repair in healthy tissue.

Researcher
Xiao-Ping Zhang purifies the repair protein Rad51 in yeast.