A study published yesterday in the Journal of Biological Chemistry has identified cellular processes that appear to supercharge both the growth and shrinkage of the chemical "caps" on chromosomes, called telomeres, that are associated with aging. The research, focused on two enzymes in yeast, could lead to new insights on stopping runaway cellular growth in cancer tumors, as well as the treatment of premature aging disorders such as progeria (aka "Benjamin Button disease").
"This work confirms that two specific enzymes—called helicases—are involved in telomere maintenance, and demonstrates they're even stronger in combination," said senior author Matthew Bochman, an associate professor at Indiana University. "This is significant since dysfunction in telomere maintenance has been found in 100 percent of cancers. Literally, 100 percent. So, it's very likely they play a role in the disease."
Telomeres shorten slowly over the lifespan of healthy people as part of the natural aging process. In cancer cells, telomeres never grow shorter—resulting in uncontrolled cellular replication. Conversely, in people with premature aging disorders, telomeres rapidly shrink, resulting in death from "old age" in the late teenage years.
This study specifically found that telomere maintenance in yeast could be disrupted by two enzymes, Hrq1 and Pif1. These enzymes are helicases—enzymes that unwind double-stranded DNA into a single strand for the purposes of replication, recombination, and repair. Their complete mechanisms of action are not fully known, but this study found that they can combine to create a "super inhibitor" or a "super stimulator" of telomere growth.
In humans, the RecQ4 helicase functions similarly to the Hrq1 helicase in yeast. The Pif1 helicase is the same in both species. Mutations of the Pif1 helicase have been linked to several types of cancer, including common forms such as breast, ovarian and colon cancer. Mutations in the RecQ4 helicase have been linked to three different diseases associated with predispositions for cancer.
This work may help scientists better understand whether certain cancers involve errors in DNA recombination, DNA repair, or telomere maintenance—or some other mechanistic problem. This, in turn, could lead to the discovery of new methods to disrupt or harness these processes with drugs or other therapies.