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Researchers identify protein-telomere interactions that could be key in treating cancer
September 01, 2009A 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. Since this RNA also facilitates the formation of DNA at telomeres-a process that can protect aging cells and destabilize tumor cells-manipulating its expression may be useful in treating cancer and other diseases.
The steady shortening of telomeres with each replication in somatic cells is linked to cellular aging, genetic instability, and tumor formation. This is because telomeres eventually "run out" after a certain number of cell divisions, resulting in the loss of vital genetic information from the cell's chromosome with future divisions. Scientists recently identified telomere-repeat-encoding RNA (TERRA) as an integral component of DNA within the telomeres of multiple species. The Wistar team demonstrated how TERRA mediates and partially stabilizes interactions between telomeric proteins that play essential roles in DNA replication.
"TERRA is a major component in helping protect the genome at a very sensitive place, the telomeres," said senior author Paul M. Lieberman, Ph.D., a professor in Wistar's Gene Expression and Regulation Program. "By managing TERRA levels we have the potential to regulate cellular aging and to impair the functioning of cancer cells."
TERRA associates with telomeric factors, but its precise function and mechanism of localization at telomeres had been largely unknown. In a study published on-line on August 27 in Molecular Cell, the Wistar scientists, led by Lieberman, describe how they discovered the telomere proteins that interact with TERRA and the processes by which they do so. In cell cultures, through RNA affinity purification, a process that isolates a single type of protein from a complex mixture, the team identified telomeric proteins (Shelterin components TRF1 and TRF2, and origin recognition complex subunits ORC1, ORC2, and ORC4) that bound to a TERRA oligonucleotide sequence but not to control oligonucleotides. Using RNA chromatin immunoprecipitation assays (ChIPs), in which specific pieces of RNA are isolated from bound proteins, the team discovered that TERRA is bound by telomeric proteins indicating that TERRA was a component of the Shelterin complex. The findings provide important clues that point to strategies for altering the expression of TERRA as a means to treat cancer and other diseases of aging, Lieberman says.
The Wistar Institute
TERRA associates with telomeric factors, but its precise function and mechanism of localization at telomeres had been largely unknown. In a study published on-line on August 27 in Molecular Cell, the Wistar scientists, led by Lieberman, describe how they discovered the telomere proteins that interact with TERRA and the processes by which they do so. In cell cultures, through RNA affinity purification, a process that isolates a single type of protein from a complex mixture, the team identified telomeric proteins (Shelterin components TRF1 and TRF2, and origin recognition complex subunits ORC1, ORC2, and ORC4) that bound to a TERRA oligonucleotide sequence but not to control oligonucleotides. Using RNA chromatin immunoprecipitation assays (ChIPs), in which specific pieces of RNA are isolated from bound proteins, the team discovered that TERRA is bound by telomeric proteins indicating that TERRA was a component of the Shelterin complex. The findings provide important clues that point to strategies for altering the expression of TERRA as a means to treat cancer and other diseases of aging, Lieberman says.
The Wistar Institute
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 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.
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.
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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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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: 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 Stellar Sea Telomere (Primary Contributor) |
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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 by Telomere |
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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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Zoetosis Telomere (Primary Contributor) |
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AgeTone DNA Skin Care Cream by CharPei Skin Care (A Geromatrix Co.) This unique telomere based cream corrects all signs of skin aging. By promoting the skins natural protection and repair factors involved in detoxification, anti-stress, telomere maintenance which is crucial to the life of the cell and DNA repair. AgeToneTM DNA Repair Cream helps prevent the senescence of cells; enhancing cell function, improving the quality of the tissue, and extending the youthspan of the skin to reduce all visible signs of aging not just wrinkles. |
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