Cornell researchers have developed a new technique to understand the actions of key proteins required for cancer cells to proliferate.
The technique will help guide the development of drugs currently in clinical trials for anti-cancer treatments that inhibit this class of proteins, called kinases.
The study, published March 5 in the journal Molecular Cell, focuses on a few kinases – mainly ATR and ATM – that are involved in detecting and triggering responses to DNA damage in all human cells. Since our DNA may be replicated as many as 20 trillion times from fertilized egg through adulthood, there are many occasions for error and the need for repair.
“The ATR protein is well-known to detect damage in our DNA and coordinate a response that ensures the efficient repair of the damage before the cell divides into two distinct cells,” said Marcus Smolka, associate professor of molecular biology and genetics in the Weill Institute for Cell and Molecular Biology, and senior author of the paper. Francisco Meirelles Bastos de Oliveira, a former postdoctoral researcher, is the paper’s first author, along with graduate student Dongsung Kim, both in Smolka’s lab.
Damage that occurs during replication may be compared to a water pipe breaking in a municipality, said Smolka. “You need a system to detect when a water pipe breaks, and you need a group that makes and coordinates decisions to turn off the water, to notify people in the neighborhood, and to call a repair group,” Smolka said. In this analogy, ATR and ATM function as the group that detects and signals other entities for an appropriate response.
In cancer cells, which reproduce very quickly, there is a great deal of DNA damage, as if “hundreds of water pipes are broken” at once, Smolka said. “Cancer cells highly depend on ATR to survive,” he added.
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The study was funded by National Institutes of Health, American Cancer Society and the Cornell Fleming Research Fellowship.
