ATM kinase, an enzyme known to be involved in DNA repair, is required for telomere elongation, according to a study published in Cell Reports. The results could have implications for diverse diseases, from cancer, which is typically linked to overly long telomeres, to lung and bone marrow disorders that are associated with shortened telomeres.
“We’ve known for a long time that telomerase doesn’t tell the whole story of why chromosomes’ telomeres are a given length, but with the tools we had, it was difficult to figure out which proteins were responsible for getting telomerase to do its work,” Carol Greider, a director at the Johns Hopkins Institute for Basic Biomedical Sciences and a corecipient of the 2009 Nobel Prize in Physiology or Medicine for the discovery of telomerase, said in a press release.
Identifying enzymes involved in maintaining telomere length in mammalian cells has been slow going, requiring blocking individual proteins’ functions then growing the cells in the lab and looking for differences in telomere length between experimental and control cells. In addition to taking at least three months before detectable differences arose, blocking proteins that were required for cell survival would kill the cells before such differences could be seen.
Greider and her colleagues devised a way to expedite the process by cutting telomeres, then looking for elongation by telomerase—a strategy that has been previously used in yeast cells. Using this method, which the researchers dubbed addition of de novo initiated telomeres (ADDIT), the group investigated the role of ATM kinase. Blocking ATM kinase in mouse cells, then cutting down the telomeres, the group found that the enzyme was required to lengthen the chromosome caps—a result verified using the old, three-month-long method. Conversely, activating ATM kinase with a PARP1 inhibitor spurred telomere elongation.
Greider’s team now plans to further explore the role of ATM kinase in telomere elongation and look for other components important in telomere maintenance. “The potential applications are very exciting,” Stella Suyong Lee, a graduate student in the Greider lab who spearheaded the development of ADDIT, said in the release. “Ultimately ADDIT can help us understand how cells strike a balance between aging and the uncontrolled cell growth of cancer, which is very intriguing.”