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Researchers examine mechanisms that help cancer cells proliferate
September 02, 2009A 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.
Most cells in the human body divide only a certain number of times, via a countdown mechanism that stops them. When the controlling process goes wrong, the cells divide indefinitely, contributing to cancer growth.
The number of times a cell divides is determined by special segments of DNA called telomeres, which are located at the ends of each chromosome. Every time a cell divides, the telomeres get shorter. When they are reduced to a certain length, the cell stops dividing.
In the new study, UT Southwestern researchers used both normal and cancerous human cells to examine closely how telomeres behave during cell division.
As a cell prepares to divide into two new cells, its ladder-shaped DNA "unzips," creating two halves, each resembling a single upright of a ladder with a set of half-length rungs. Fresh genetic material then fills in the rungs and a second upright. This process creates two identical sets of chromosomes that will be allotted between the two cells.
From earlier studies on model organisms such as yeast, scientists thought that all telomeres replicated late in the stage of overall DNA replication, and by the same processes. The new study suggests that telomeres replicate at various times during this stage, except for a final step that is not completed until the very end, via a different, unknown mechanism.
"Interfering with replication of telomeres might provide a way to halt uncontrolled spread of cancer cells," said Dr. Woodring Wright, professor of cell biology at
UT Southwestern and co-senior author of the paper.
The researchers also examined an enzyme called telomerase, which "rebuilds" telomeres so they do not get shorter and signals the cell to stop dividing. Normally, telomerase is only active in cells such as stem cells and dividing immune cells, which must reproduce constantly.
But telomerase also has a dark side: When active in cancer cells, it enables unlimited growth, a hallmark of cancer.
It had been thought that telomerase only works on the shortest telomeres in a cell, but in the new study, the UT Southwestern researchers found that telomerase rebuilds most or all of the telomeres in a cell for each division, not just the shortest ones, as had been thought.
"Understanding ways to inhibit this telomerase mechanism might lead to novel anticancer therapies," said Dr. Jerry Shay, professor of cell biology and co-senior author of the paper.
Clinical trials using a drug that blocks telomerase are already under way at
UT Southwestern for lung cancer and chronic lymphocytic leukemia.
The new study was possible because the researchers developed a way to examine the very ends of telomeres after a single cell division. Previous research in the field required multiple cell divisions to detect such changes.
"Now that we can look at what telomerase is doing in a single cell-division cycle, there is potential for a tremendous number of follow-up studies," Dr. Wright said.
Other UT Southwestern researchers involved in the study were lead author Dr.Yong Zhao, postdoctoral researcher in cell biology; Dr. Agnel Sfeir, former graduate student in integrative biology; Dr. Ying Zou, former graduate student in genetics and development; graduate student Christen Buseman; and graduate student Tracy Chow.
The research was funded by the National Institutes of Health, the American Federation for Aging Research and the Department of Defense Breast Cancer Program.
Visit www.utsouthwestern.org/cancercenter to learn more about UT Southwestern's clinical services in cancer.
The University of Texas Southwestern Medical Center at Dallas
In the new study, UT Southwestern researchers used both normal and cancerous human cells to examine closely how telomeres behave during cell division.
As a cell prepares to divide into two new cells, its ladder-shaped DNA "unzips," creating two halves, each resembling a single upright of a ladder with a set of half-length rungs. Fresh genetic material then fills in the rungs and a second upright. This process creates two identical sets of chromosomes that will be allotted between the two cells.
From earlier studies on model organisms such as yeast, scientists thought that all telomeres replicated late in the stage of overall DNA replication, and by the same processes. The new study suggests that telomeres replicate at various times during this stage, except for a final step that is not completed until the very end, via a different, unknown mechanism.
"Interfering with replication of telomeres might provide a way to halt uncontrolled spread of cancer cells," said Dr. Woodring Wright, professor of cell biology at
UT Southwestern and co-senior author of the paper.
The researchers also examined an enzyme called telomerase, which "rebuilds" telomeres so they do not get shorter and signals the cell to stop dividing. Normally, telomerase is only active in cells such as stem cells and dividing immune cells, which must reproduce constantly.
But telomerase also has a dark side: When active in cancer cells, it enables unlimited growth, a hallmark of cancer.
It had been thought that telomerase only works on the shortest telomeres in a cell, but in the new study, the UT Southwestern researchers found that telomerase rebuilds most or all of the telomeres in a cell for each division, not just the shortest ones, as had been thought.
"Understanding ways to inhibit this telomerase mechanism might lead to novel anticancer therapies," said Dr. Jerry Shay, professor of cell biology and co-senior author of the paper.
Clinical trials using a drug that blocks telomerase are already under way at
UT Southwestern for lung cancer and chronic lymphocytic leukemia.
The new study was possible because the researchers developed a way to examine the very ends of telomeres after a single cell division. Previous research in the field required multiple cell divisions to detect such changes.
"Now that we can look at what telomerase is doing in a single cell-division cycle, there is potential for a tremendous number of follow-up studies," Dr. Wright said.
Other UT Southwestern researchers involved in the study were lead author Dr.Yong Zhao, postdoctoral researcher in cell biology; Dr. Agnel Sfeir, former graduate student in integrative biology; Dr. Ying Zou, former graduate student in genetics and development; graduate student Christen Buseman; and graduate student Tracy Chow.
The research was funded by the National Institutes of Health, the American Federation for Aging Research and the Department of Defense Breast Cancer Program.
Visit www.utsouthwestern.org/cancercenter to learn more about UT Southwestern's clinical services in cancer.
The University of Texas Southwestern Medical Center at Dallas
Telomeres Current Events and Telomeres News RSSChromosomes dance and pair up on the nuclear membrane
Meiosis - the pairing and recombination of chromosomes, followed by segregation of half to each egg or sperm cell - is a major crossroads in all organisms reproducing sexually.
Common weed could provide clues on aging and cancer
A common weed and human cancer cells could provide some very uncommon details about DNA structure and its relationship with telomeres and how they affect cellular aging and cancer, according to a team led by scientists from Texas A&M University and the University of Cincinnati (UC).
Mice regain ability to extend telomeres suggesting potential for dyskeratosis congenita therapy
The human genetic disease dyskeratosis congenita (DKC) is an autosomal dominant disease that leads to abnormalities in tissues with a rapid cell turnover - the skin, nails, bone marrow, lungs and gut.
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.
Baumann Lab demonstrates role of protein in distinguishing chromosome ends from DNA breaks
The Stowers Institute's Baumann Lab has demonstrated how human cells protect chromosome ends from misguided repairs that can lead to cancer.
Researchers identify protein-telomere interactions that could be key in treating cancer
A team of researchers from The Wistar Institute have shown that a large non-coding RNA in mammals and yeast plays a central role in helping maintain telomeres, the tips of chromosomes that contain important genetic information and help regulate cell division.
Protein plays unexpected role protecting chromosome tips
A protein specialist that opens the genomic door for DNA repair and gene expression also turns out to be a multi-tasking workhorse that protects the tips of chromosomes and dabbles in a protein-destruction complex, a team lead by researchers at The University of Texas M. D. Anderson Cancer Center reports in the Aug. 13 edition of Molecular Cell.
Protein complex key in avoiding DNA repair mistakes, cancer
As the body creates antibodies to fight invaders, a three-protein DNA repair complex called MRN is crucial for a normal gene-shuffling process to proceed properly, University of Michigan research shows.
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.
More Telomeres Current Events and Telomeres News Articles
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Elizabeth Blackburn and the Story of Telomeres: Deciphering the Ends of DNA by Catherine Brady (Author) Molecular biologist Elizabeth Blackburn—one of Time magazine’s 100 “Most Influential People in the World” in 2007—made headlines in 2004 when she was dismissed from the President's Council on Bioethics after objecting to the council's call for a moratorium on stem cell research and protesting the suppression of relevant scientific evidence in its final report. But it is Blackburn's groundbreaking work on telomeric DNA, which launched the field of telomere research, that will have the more profound and long-lasting effect on science and society. In this compelling biography, Catherine Brady tells the story of Elizabeth Blackburn's life and work and the emergence of a new field of scientific research on the specialized ends of chromosomes and the telomerase enzyme that extends... |
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Telomeres, Second Edition (Cold Spring Harbor Monograph Series) by Vicki Lundblad (Author), Elizabeth Blackburn (Author), Vicki Lundblad (Editor), Elizabeth Blackburn (Editor), Titia de Lange (Editor) An uptodate survey of the current exciting state of telomere biology. Telomeresspecialized structures found at the ends of chromosomes are essential for maintaining the integrity of chromosomes and their faithful duplication during cell division. Chapters in this volume cover telomere structure and function in a range of organisms, focusing on how they are maintained, their roles in cell division and gene expression, and how deficiencies in these structures contribute to cancers and other diseases and even aging. |
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Telomeres: Function, Shortening and Lengthening by Leonardo Mancini (Editor) Telomeres are a region of repetitive DNA at the end of chromosomes, which protects the end of the chromosome from destruction. They protect chromosome ends from degradation and thus prevent chromosome end fusion. This book describes the relevance of telomeres in the human ageing process and the telomere defects that play a role in the premature aging process. Dysfunctional telomeres that can promote chromosome instability, leading to DNA amplifications and terminal deletions, cell cycle arrest and cell death, are also described. The biology and function of both telomeres and telomerase are described in this book. The possible connection between telomeres, ageing and senescence, as well as the many disorders and chronic diseases where telomere biology seems to be important are addressed,... |
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The Telomere by David Kipling (Author) Telomeres--specialized structures at ends of linear chromosomes--serve a fascinating range of functions that molecular biologists and geneticists are only beginning to understand and exploit. For example, telomeres distinguish the natural end of a chromosome from a simple double-strand break, stabilize chromosomes by protecting them from fusion or activating cell cycle checkpoints, and provide mechanisms to compensate for the loss of terminal DNA sequence that occurs when linear DNA molecules are replicated. This book--the first to cover this exciting and rapidly expanding field--integrates the increasingly disparate strands of telomere research to provide an invaluable survey of the subject. Topics include the role of telomeres in nuclear organization; telomere DNA sequence and unusual... |
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The Stellar Sea Telomere (Primary Contributor) |
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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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The Stellar Sea by Telomere |
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Origin and Evolution of Telomeres (Molecular Biology Intelligence Unit) by Jozef Nosek (Author) | |
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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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