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UGA researchers discover mechanism that explains how cancer enzyme winds up on ends of chromosomes
July 11, 2008Human cancer cells divide and conquer. Unless physicians can control that division with surgery, chemotherapy or radiation, the wildly dividing cells will eventually destroy a person's life.
Researchers have known for some time that an enzyme called telomerase is crucial to cancer's progress. Now, for the first time, researchers at the University of Georgia's Franklin College of Arts and Sciences have shown a mechanism that explains how two essential components of human telomerase-normally active only in early prenatal development but turned back on during cancer growth-are "recruited" from distinct sites in the cell to the telomere, an area at the end of a chromosome that normally protects it from destruction.
"Telomerase is reactivated in more than 90 percent of human cancers," said Michael Terns, professor of biochemistry and molecular biology and genetics at UGA, "and the fact that telomerase keeps these telomeres growing when it should be inactive is crucial for the proliferation of cancer. That makes telomerase a very promising target for a potential drug to stop cancers from spreading."
The research was just published in the journal Molecular Biology of the Cell. Other authors on the paper were Rebecca Terns, a senior research scientist also in UGA's department of biochemistry and molecular biology (Michael and Rebecca Terns are a husband-wife team); Rebecca Tomlinson, a former doctoral student in the Terns Lab; Eladio Abreu, a current graduate student in the Terns lab; Tania Ziegler, also a former member of the Terns lab, now pursuing an M.D. degree; Hinh Ly of Emory University; and Christopher Counter of Duke University Medical Center. Rebecca and Michael Terns are also members of the University of Georgia Cancer Center.
The two essential components of human telomerase are telomerase RNA and telomerase reverse transcriptase. They are "recruited" to telomeres during what is called the "S phase" (for synthesis) of the cell cycle when DNA replication or synthesis occurs.
"What we have found is that during the remainder of the cell cycle, telomerase RNA is found primarily in rather mysterious and, until recently, little-understood structures called Cajal bodies," said Rebecca Terns. "Though science has known about Cajal [pronounced Ca-HAHL] bodies for more than a hundred years, what we have discovered is that the localization of telomerase RNA to Cajal bodies and telomeres is specific to cancer cells where telomerase is active."
The new research shows for the first time that the trafficking of telomerase RNA to both telomeres and Cajal bodies depends on the presence of telomerase reverse transcriptase.
The Terns lab took advantage of the differences between normal and cancer cells of many kinds to better understand the trafficking of telomerase RNA.
"We examined a variety of factors that differ between normal and cancer cells in order to identify factors that impact human telomerase localization," said Michael Terns. "Our results indicate that human reverse transcriptase is a key determinant in human telomerase trafficking and is essential for the localization of telomerase RNA both to Cajal bodies and telomeres."
While all this jargon-filled science may sound difficult to understand, the discovery could lead to new ways to attack cancers by blocking their ability to grow. While that is years down the road, the new understanding of how this crucial biological action in the human body takes place will at the very least open new avenues of investigation into why and how cancer cells continue to grow and take the human toll they do every day.
University of Georgia
The research was just published in the journal Molecular Biology of the Cell. Other authors on the paper were Rebecca Terns, a senior research scientist also in UGA's department of biochemistry and molecular biology (Michael and Rebecca Terns are a husband-wife team); Rebecca Tomlinson, a former doctoral student in the Terns Lab; Eladio Abreu, a current graduate student in the Terns lab; Tania Ziegler, also a former member of the Terns lab, now pursuing an M.D. degree; Hinh Ly of Emory University; and Christopher Counter of Duke University Medical Center. Rebecca and Michael Terns are also members of the University of Georgia Cancer Center.
The two essential components of human telomerase are telomerase RNA and telomerase reverse transcriptase. They are "recruited" to telomeres during what is called the "S phase" (for synthesis) of the cell cycle when DNA replication or synthesis occurs.
"What we have found is that during the remainder of the cell cycle, telomerase RNA is found primarily in rather mysterious and, until recently, little-understood structures called Cajal bodies," said Rebecca Terns. "Though science has known about Cajal [pronounced Ca-HAHL] bodies for more than a hundred years, what we have discovered is that the localization of telomerase RNA to Cajal bodies and telomeres is specific to cancer cells where telomerase is active."
The new research shows for the first time that the trafficking of telomerase RNA to both telomeres and Cajal bodies depends on the presence of telomerase reverse transcriptase.
The Terns lab took advantage of the differences between normal and cancer cells of many kinds to better understand the trafficking of telomerase RNA.
"We examined a variety of factors that differ between normal and cancer cells in order to identify factors that impact human telomerase localization," said Michael Terns. "Our results indicate that human reverse transcriptase is a key determinant in human telomerase trafficking and is essential for the localization of telomerase RNA both to Cajal bodies and telomeres."
While all this jargon-filled science may sound difficult to understand, the discovery could lead to new ways to attack cancers by blocking their ability to grow. While that is years down the road, the new understanding of how this crucial biological action in the human body takes place will at the very least open new avenues of investigation into why and how cancer cells continue to grow and take the human toll they do every day.
University of Georgia
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National Science Foundation congratulates Nobel Laureates in medicine/physiology, chemistry and economics
The National Science Foundation (NSF) congratulates the 2009 Nobel laureates, particularly those who have received NSF funding over the years: Jack W. Szostak, who shared the prize in physiology or medicine; Thomas A. Steitz, who shared the prize in chemistry; and Elinor Ostrom and Oliver E. Williamson who earned the Sveriges Riksbank Prize in economic sciences in memory of Alfred Nobel 2009.
Researchers examine mechanisms that help cancer cells proliferate
A process that limits the number of times a cell divides works much differently than had been thought, opening the door to potential new anticancer therapies, researchers at UT Southwestern Medical Center report in the Aug. 7 issue of the journal Cell.
Handle with care: Telomeres resemble DNA fragile sites
Telomeres, the repetitive sequences of DNA at the ends of linear chromosomes, have an important function: They protect vulnerable chromosome ends from molecular attack.
Variations in 5 genes raise risk for most common brain tumors
Common genetic variations spread across five genes raise a person's risk of developing the most frequent type of brain tumor, an international research team reports online in Nature Genetics.
Immune cells from patients with rheumatoid arthritis have prematurely aged chromosomes
Telomeres, structures that cap the ends of cells' chromosomes, grow shorter with each round of cell division unless a specialized enzyme replenishes them. Maintaining telomeres is thought to be important for healthy aging and cancer prevention.
Testes stem cell can change into other body tissues, Stanford/UCSF study shows
Scientists at the Stanford University School of Medicine and at UC-San Francisco have succeeded in isolating stem cells from human testes.
UT Southwestern researchers identify gene linked to inherited form of fatal lung disease
Researchers at UT Southwestern Medical Center have determined that a mutation in a gene known for its role in defending the lungs against invading pathogens is responsible for some inherited cases of a lethal lung disease affecting older adults. The same mutation may also be associated with lung cancer, the researchers said.
Researchers use chemical from medicinal plants to fight HIV
Like other kinds of cells, immune cells lose the ability to divide as they age because a part of their chromosomes known as a telomere becomes progressively shorter with cell division. As a result, the cell changes in many ways, and its disease fighting ability is compromised.
Scientists identify possible cause of endometriosis
Endometriosis is a condition whereby patches of the inner lining of the womb appear in parts of the body other than the womb cavity. It can cause severe pain and affects approximately 15% of women of reproductive age. Endometriosis is also associated with infertility, with 50% of infertile women affected by the condition.
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Jan Marini Age Intervention REGENERATION BOOSTER for Science-Based Compound for Dramatically Younger Looking Skin by Jan Marini Skin Research Aging skin is still a reality, but the key to aging may reside in the ability to stabilize telomeres by allowing cells to "reset their aging clocks." Now our extraordinary new skin care compound captures the emerging science of topical Telomerase Enzyme as a realistic science-based option for dramatically younger looking skin. -Age Intervention Regeneration Booster combines Telomerase Enzyme in combination with anti-inflammatory agents, select peptides and other proven significant skin enhancing ingredients. An independent clinical study demonstrates measurable, significant and lasting improvements in the appearance of: Lines and wrinkles Elasticity Firmness Texture Discoloration Overall radiance, suppleness and hydration Each program consists of six mini-bottles, including one... |
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Telomeres and Telomerase in Aging, Disease, and Cancer: Molecular Mechanisms of Adult Stem Cell Ageing by K. Lenhard Rudolph (Author), K. Lenhard Rudolph (Editor) The understanding of the molecular mechanisms underlying the ageing process is essential to improve quality of life and health span in the growing populations of the elderly. Telomere shortening represents one of the basic aspects of ageing and telomere dysfunction could contribute to the accumulation of DNA damage during ageing. This book summarizes experimental evidence and clinical data indicating that telomere dysfunction influences human ageing, diseases and cancer. In addition, the book describes our current knowledge on checkpoints that limit cellular lifespan (senescence) and survival (apoptosis, crisis) in response to telomere dysfunction. A special focus of the book is on adult stem cells. There is emerging evidence that adult stem cell ageing impairs... |
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Telomeres and Telomerase: Methods and Protocols (Methods in Molecular Biology) by John A. Double (Author), Michael J. Thompson (Author) John A. Double and Michael J. Thompson have collected a critically important series of novel and essential techniques for studying telomeres and telomerase. These readily reproducible methods provide cutting-edge tools to identify, measure, and analyze telomeres, to determine telomerase expression at the RNA level, to determine telomerase activity, and to detect potential modifiers of this activity. The techniques for assaying telomerase activity range from standard radiological TRAP assays to nonradioactive methods, from non PCR-based methods to techniques using real-time PCR. Telomeres and Telomerase: Methods and Protocols provides the core array of productive techniques needed today to develop telomerase inhibitors or diagnostic/prognostic telomerase markers. |
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Telomeres and Telomerase - Symposium No. 211 by CIBA Foundation Symposium (Author) Telomeres and Telomerase Chairman: Sydney Brenner 1997 Telomeres are the protective genetic elements located at the ends of chromosomes and are essential for correct chromosomal structure and function. They are not fully replicated by the conventional DNA polymerase system because DNA synthesis occurs only in the 5??? to 3??? direction and requires an RNA primer for initiation. Consequently, cells require a special enzyme to maintain the telomeric ends of chromosomes during each round of replication. This enzyme, telomerase, is a ribonucleoprotein that extends chromosome ends by adding short stretches of nucleotide repeats using a portion of its integral RNA component as the template. Recently, much excitement has been generated by the suggestion that telomerase, or rather the absence of... |
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Telomere and Telomerase Modulation by the Mammalian Rad9/Rad1/Hus1 DNA-Damage-Checkpoint Complex [A short communication from: Current Biology by S. Francia (Author), R.S. Weiss (Author), M.P. Hande (Author), R. Freire (Author), d'A (Author) This digital document is a journal article from Current Biology, published by Elsevier in 2006. The article is delivered in HTML format and is available in your Amazon.com Media Library immediately after purchase. You can view it with any web browser. Abstract: Telomeres, the termini of linear chromosomes, are exceptional in that they are DNA ends that do not normally trigger a DNA-damage response (DDR) and are compatible with normal cellular proliferation. Mammalian telomeres are nevertheless a physiological substrate of the DDR apparatus, as shown by the fact that the inactivation of genes encoding certain DDR factors results in telomere dysfunction [1-3]. However, how DDR factors are integrated with telomere physiology, including telomere length regulation by the specialized... |
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Telomeres and Telomerase in Cancer (Cancer Drug Discovery and Development) by Keiko Hiyama (Editor) Telomerase, an enzyme that maintains telomeres and endows eukaryotic cells with immortality, was first discovered in tetrahymena in 1985. In 1990s, it was proven that this enzyme also plays a key role in the infinite proliferation of human cancer cells. Now telomere and telomerase are widely accepted as important factors involved in cancer biology, and as promising diagnostic tools and therapeutic targets. Recently, role of telomerase in “cancer stem cells” has become another attractive story. Until now, there are several good books on telomere and telomerase focusing on biology in ciliates, yeasts, and mouse or basic sciences in human, providing basic scientists or students with updated knowledge. |
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Telomerase, Aging and Disease, Volume 8 (Advances in Cell Aging and Gerontology) by M.P. Mattson (Editor) This volume of Advances in Cell Aging and Gerontology critically reviews the rapidly advancing area of telomerase research with a focus at the molecular and cellular levels. The clearly established function of telomerase is to maintain chromosome ends during successive rounds of cell division by adding a six base DNA repeat on to the telomeric ends of chromosomes. As presented in the chapters of this volume, the mechanisms that regulate telomerase expression and activity are complex. Moreover, emerging data suggest additional roles for telomerase in the regulation of cell differentiation and survival.
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Telomeres and Telomerase: Reprint of Cytogenetic and Genome Research, Vol. 122, No. 3-4, 2008 by Predrag Slijepcevic (Editor) |
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Extended life-spans. (includes related articles on longer lifespan and on telomerase discovery): An article from: The Futurist by Marvin Cetron (Author), Owen Davies (Author) This digital document is an article from The Futurist, published by World Future Society on April 1, 1998. The length of the article is 5684 words. The page length shown above is based on a typical 300-word page. The article is delivered in HTML format and is available in your Amazon.com Digital Locker immediately after purchase. You can view it with any web browser. From the supplier: The discovery of melatonin as the hormone that has the ability to retard aging created an excitement in the scientific world as visions of humans living until the age of 120, 150, 200 or more can be made possible. Society, however, should prepare for the consequences of these breakthroughs. Citation Details Title: Extended life-spans. (includes related articles on longer lifespan and on... | |
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The Telomerase Project by William A. Gilmartin (Author) A secret project inside a cancer research company results in a remarkable discovery--a way to stop and reverse the aging process! But a power hungry venture capitalist and a government agency want to control it. The scientist behind the discovery is forced to disappear. His daughter and best friend become bait in a deadly manhunt that starts in Silicon Valley, moves into the high mountains of Colorado and ends in Washington D.C. Is the world ready for life ever lasting? Who gets to decide? |
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