Their latest findings, published today in Molecular Cell, demonstrate that telomerase repairs chromosomes in one of two ways – depending on whether a cell is dividing normally or if the cell is under stress from enzyme inhibition – and could lead to new or improved cancer-fighting therapies that promote inhibition of this enzyme.
“It’s a significant advance in our understanding of how telomerase works,” said Dr. Woodring Wright, professor of cell biology and senior author of the study. “Our goal is to identify new targets for inhibiting telomerase.”
The number of times a cell divides is determined by telomeres, protective caps on the ends of chromosomes that indicate cell age. Every time a cell divides, the telomeres shorten. When telomeres shrink to a certain length, the cell either dies or stops dividing. In cancer cells, the enzyme telomerase keeps rebuilding the telomeres, so the cell never receives the cue to stop dividing.
Although telomerase was discovered in 1985, exactly how this enzyme repairs telomeres to enable cancer cells to divide and grow was largely unknown. Until now, researchers didn’t know how many telomerase molecules went into action at the telomeres and under what conditions.
“It’s a single molecule under normal cancer growth conditions, but if you shorten telomeres artificially by inhibiting telomerase, now it’s more than one molecule acting on the ends of the telomeres,” Dr. Wright said of the study’s findings.
When acting as a single molecule at the telomeres, telomerase adds about 60 nucleotide molecules “in one fell swoop to the end of the chromosome,” Dr. Wright said.
Researchers also discovered that structures in cells called Cajal bodies help process telomerase during chromosome-repair activity. Cajal bodies assemble ribonucleic acid (RNA) within proteins.
“Telomerase uses this RNA in order to add the sequences onto the end, and this complex is assembled or modified in some way in these Cajal bodies,” Dr. Wright said.
UT Southwestern scientists next will work to pinpoint the precise molecules that bring telomerase to telomeres for potential development of inhibitors that would be new cancer drugs.
“We now need to find the molecules that are doing that as targets for additional inhibitors,” Dr. Wright said. “We have identified the step, but we haven’t yet identified the molecules involved.”
One drug that blocks telomerase, Imetelstat or GRN163L, was developed by the biotechnology company Geron with help from Drs. Wright and Jerry Shay, professor of cell biology. That drug, tested at UT Southwestern, is currently in clinical trials for treatment of several types of cancer.
Other UT Southwestern researchers involved in this study were lead author and assistant instructor Dr. Yong Zhao; Dr. Jinyong Kim and Dr. Guido Stadler, both postdoctoral fellows in cell biology; Ugur Eskiocak, a student research assistant in cell biology; and Dr. Shay. Biochemistry and molecular biology and genetics researchers at the University of Georgia also participated.
The work was supported by grants from the National Institute on Aging, National Cancer Institute, American Federation for Aging Research and the National Institutes of Health.
Visit www.utsouthwestern.org/cancer to learn more about UT Southwestern’s clinical services in cancer.This news release is available on our World Wide Web home page at
Debbie Bolles | Newswise Science News
Scientists discovered 20 new gnat species in Brazil
24.09.2018 | Estonian Research Council
Brought to light – chromobodies reveal changes in endogenous protein concentration in living cells
21.09.2018 | NMI Naturwissenschaftliches und Medizinisches Institut an der Universität Tübingen
The building blocks of matter in our universe were formed in the first 10 microseconds of its existence, according to the currently accepted scientific picture. After the Big Bang about 13.7 billion years ago, matter consisted mainly of quarks and gluons, two types of elementary particles whose interactions are governed by quantum chromodynamics (QCD), the theory of strong interaction. In the early universe, these particles moved (nearly) freely in a quark-gluon plasma.
This is a joint press release of University Muenster and Heidelberg as well as the GSI Helmholtzzentrum für Schwerionenforschung in Darmstadt.
Then, in a phase transition, they combined and formed hadrons, among them the building blocks of atomic nuclei, protons and neutrons. In the current issue of...
Thin-film solar cells made of crystalline silicon are inexpensive and achieve efficiencies of a good 14 percent. However, they could do even better if their shiny surfaces reflected less light. A team led by Prof. Christiane Becker from the Helmholtz-Zentrum Berlin (HZB) has now patented a sophisticated new solution to this problem.
"It is not enough simply to bring more light into the cell," says Christiane Becker. Such surface structures can even ultimately reduce the efficiency by...
A study in the journal Bulletin of Marine Science describes a new, blood-red species of octocoral found in Panama. The species in the genus Thesea was discovered in the threatened low-light reef environment on Hannibal Bank, 60 kilometers off mainland Pacific Panama, by researchers at the Smithsonian Tropical Research Institute in Panama (STRI) and the Centro de Investigación en Ciencias del Mar y Limnología (CIMAR) at the University of Costa Rica.
Scientists established the new species, Thesea dalioi, by comparing its physical traits, such as branch thickness and the bright red colony color, with the...
Scientists have succeeded in observing the first long-distance transfer of information in a magnetic group of materials known as antiferromagnets.
An international team of researchers has mapped Nemo's genome, providing the research community with an invaluable resource to decode the response of fish to...
21.09.2018 | Event News
03.09.2018 | Event News
27.08.2018 | Event News
24.09.2018 | Physics and Astronomy
24.09.2018 | Earth Sciences
24.09.2018 | Health and Medicine