New Insight into Telomere Regulation
Patricia Opresko, Ph.D.
University of Pittsburgh
Research, funded in part by NIEHS, has uncovered new details about the regulation of telomeres. These repeated DNA sequences protectively cap the ends of chromosomes and play an important role in cancer and aging.
Telomeres become shorter every time a cell divides. Once they are too short, telomeres send a signal for the cell to stop dividing permanently, which weakens the ability of tissues to regenerate and plays a role in many aging-related diseases. In contrast, most cancer cells show elevated levels of the telomere-lengthening enzyme telomerase, allowing cancer cells to divide indefinitely.
To better understand what happens to telomeres damaged by oxidative stress, the researchers examined 8-oxo-7,8-dihydro-2'-deoxyguanine (8-oxoG), a common DNA lesion caused by oxidative stress. The research revealed that when a nucleotide containing 8-oxoG was incorporated into a telomere, any further elongation stopped. By contrast, 8-oxoG lesions found within the telomeric DNA promoted telomerase activity and telomere elongation. These findings showed the mechanism by which the 8-oxoG lesion arises in telomeres dictates whether telomerase is inhibited or stimulated and thus determines whether the telomere is shortened or lengthened.
The new information revealed by this study could be useful for developing new ways to fight cancer and therapies that could help lessen the effects of aging.
Citation: Fouquerel E, Lormand J, Bose A, Lee HT, Kim GS, Li J, Sobol RW, Freudenthal BD, Myong S, Opresko PL. 2016. Oxidative guanine base damage regulates human telomerase activity. Nat Struct Mol Biol 23(12):1092-1100.
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