Research reveals how cancer-driving enzyme works

May 06, 2011

Cancer researchers at UT Southwestern Medical Center are helping unlock the cellular-level function of the telomerase enzyme, which is linked to the disease's growth.

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 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 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 .

Explore further: Students create microbe to weaken superbug

Related Stories

Scientists identify key component in cell replication

Jan 29, 2009

Last week, a presidential limousine shuttled Barack Obama to the most important job in his life. Scientists at the Stanford University School of Medicine have now identified a protein that does much the same for the telomerase ...

Short chromosomes put cancer cells in forced rest

Apr 25, 2007

A Johns Hopkins team has stopped in its tracks a form of blood cancer in mice by engineering and inactivating an enzyme, telomerase, thereby shortening the ends of chromosomes, called telomeres.

New target for cancer therapy identified

Sep 21, 2006

A new target for cancer therapy has been identified by Monash University scientists investigating the cell signalling pathways that turn on a gene involved in cancer development.

Recommended for you

How calcium regulates mitochondrial carrier proteins

15 hours ago

Mitochondrial carriers are a family of proteins that play the key role of transporting a chemically diverse range of molecules across the inner mitochondrial membrane. Mitochondrial aspartate/glutamate carriers are part of ...

Team conducts unprecedented analysis of microbial ecosystem

16 hours ago

An international team of scientists from the Translational Genomics Research Institute (TGen) and The Luxembourg Centre for Systems Biomedicine (LCSB) have completed a first-of-its-kind microbial analysis of a biological ...

Students create microbe to weaken superbug

Nov 25, 2014

A team of undergraduate students from the University of Waterloo have designed a synthetic organism that may one day help doctors treat MRSA, an antibiotic-resistant superbug.

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.