Telomere Maintenance in Human Cell Lines and Tumors without Telomerase

Clare L. Fasching, Roger R. Reddel

In eukaryotic organisms containing linear chromosomes, each chromosome end terminates in a specialized structure, referred to as a telomere, that contains Grich repetitive DNA.¹ In humans the DNA repeat unit is the six base pair (bp) sequence 5'TTAGGG3'.² The tel...

Recombinational Telomere Elongation in the Yeast Kluyveromyces lactis

Michael J. McEachern

As detailed elsewhere in this book, the functioning of human telomeres was shown to be involved in both carcinogenesis and cellular senescence. The gradual shortening of telomeres that occurs in the absence of telomerase limits the proliferative potential of cells.¹³ Regain...

Telomeres without Telomerase in Saccharomyces cerevisiae

Edward J. Louis

There are two important properties of telomeres. They must be able to overcome the inability for DNA polymerases to replicate the ends of chromosomes, the endreplication problem, and they must not treat the end of the chromosome as DNA damage, the endprotection problem. The maintenanc...

Structure and Maintenance of Chromosome Ends in Plants

Jîrí Fajkus and Ulrike Zentgraf

Let us open this chapter by answering two basic questions: which features distinguish the terminal parts of plant chromosomes from their internal regions, and what is special about plant chromosome ends with respect to those in other eukaryotes?

Like the rest of the chromosome, its t...

New Telomere Formation During the Process of Chromatin Diminution in the Parasitic univalens

Fritz Müller

Telomeres are specialized DNAprotein complexes at the end of all linear eukaryotic chromosomes that are essential for the maintenance of genome integrity. In the vast majority of eukaryotes, telomeric DNA is composed of tandem arrays of short repeated sequences that serve as binding s...

Regulation of Telomerase Activity

JunPing Liu, Siddhartha Deb, and He Li

Essential for genomic integrity and stability within the cell, telomerase plays an important role in cell proliferation and aging. Telomerase maintains the genome with its enzy matic activity catalyzing the polymerization of deoxynucleoside triphosphates along the single stranded telo...

Telomerase and Radiosensitivity of Human Tumors

Tej K. Pandita

Telomerase is a ribonucleoprotein complex that elongates telomeres. It is ubiquitous in embryonic tissues but downregulated in most of the somatic tissues. Biochemical and genetic studies have established an association between telomere maintenance and extended lifespan through telome...

Telomerase Activity in Neuroblastomas: A New Molecular Marker for Treatment

Christopher Poremba and Barbara Dockhorn Dworniczak

Neuroblastoma, a tumour derived from neural crest cells, represents the third most common pediatric cancer (accounting for approximately 710% of all childhood malignancies) and is the most common solid extracranial neoplasm of infancy and childhood, responsible for approximately 15% of a...

Telomerase in Mesothelioma: Diagnostic and Therapeutic Applications

Karl Dhaene

Malignant mesothelioma (MM) is an aggressive malignancy of the mesothelial cell (MC) lining the body cavities. In western Europe, its incidence is expected to rise till 2020 because of the widespread use of asbestos fibersthe causative agentand the decade long interval between exposure a...

Telomerase Activity in Mesenchymal Tumors

Regine Schneider Stock, Carsten Boltze, and Albert Roessner

Together with tumors of bone, soft tissue tumors form a major histogenetic class that is distinct from neoplasms of epithelial, hematopoetic, or central neurogenic origin. Although consistent chromosomal translocations specific to histological subtypes, including some rare sarcomas,^...

The Role of Telomerase DeRegulation in Keratinocyte Immortality and the Progression

E. Kenneth Parkinson

In contrast to normal keratinocytes, most advanced human head and neck squamous cell carcinomas (SCC-HNs) are immortal¹ and the immortal phenotype is associated with specific forms of genetic instability¹, the inactivation of p53 and p16^{INK4A 1,2}

Human, Mouse and Yeast Telomerase

Tara J. Moriarty and Chantal Autexier

Telomeres, the ends of chromosomes, and their associated proteins, maintain genomic stability.¹ Intact telomeres prevent the ends of chromosomes from being degraded by exonucleases, from illegitimately recombining to produce end-to-end fusions and from activating DNA damage ch...

The Significance of Quantitative Evaluation of Telomerase Activity and hTERT mRNA Expression in Colorectal Cancers

Melissa Poggesi, Stefania Gelmini, Claudia Casini Raggi, Fabio Cianchi, Rosa Valanzano, Mario Pazzagli and Claudio Orlando

Colorectal cancer is a common tumor in western countries. In the United States, during 2000, more than 130 000 new cases of colon cancer and rectal cancer were reported¹ affecting about one person in 20 and representing 15% of cancers.² Greater public awareness and ...

Linear Plasmids in Yeasts and Filamentous Fungi

Livia Civitelli and Fiorentina Ascenzioni

Plasmids are extrachromosomal molecules that replicate independently from the genome although in some cases, when they integrate into the chromosomes, replicate as a part of the genome. Plasmids were originally found in bacteria, but subsequent studies revealed their presence also in ...

Yeast Telomerases: Structure, Mechanisms and Regulation

Neal F. Lue

Because of the ability to carry out facile genetic analysis, budding yeasts have long been used as model systems for identifying factors involved in regulating telomere structure and maintenance. However, due to the lack of a suitable assay and scarcity of material, the analysis of yeast...

Roles for TERT and Telomerase in Cell Differentiation and Apoptosis

Mark P. Mattson, Peisu Zhang and Weiming Fu

High levels of telomerase activity are associated with cell proliferation during embryonic development and with cell transformation and cancers. In developing tissues levels of telomerase activity decrease as progenitor cells cease dividing and begin differentiating into the cell types t...

Mitochondrial Telomeres: Alternative Solutions to the End-Replication Problem

Jozef Nosek and Lubomir Tomaska

Linear and circular genomes may appear to be evolutionarily distant. However, there are numerous cases in which closely related organisms with nearly identical genomes can be found arranged either as a circle or as a linear molecule with specialized telomeric structures. Mitochondrial ge...

Telomerase Activity as a Marker of Tumor Cell Survival to Evaluate Sensitivity of Neoplastic Cells to Cancer Treatment

Isabella Faraoni and Enzo Bonmassar

Part of this book is dedicated to the large amount of experimental data presently available on the biochemical and molecular aspects of telomerase. Therefore no details on this enzymatic function will be mentioned in this Chapter. However it should be pointed out that telomerase is able ...

DNA Primer Extension by Telomerase

Haim Manor, Yonit Haviv and Nava Baran

Telomeres are DNA-protein complexes found at the ends of linear eukaryotic chromosomes. The telomeric complexes prevent the chromosome ends from being recognized and processed as double strand breaks (for a review, see ref. 1). In most eukaryotes, the telomeric DNA consists of short repe...

The Makings of Telomerases

Joachim Lingner and Christian Wenz

The discovery of the cellular reverse transcriptase known as 'telomerase' in extracts from the singlecelled ciliate Tetrahymena thermophila by Carol Greider and Elizabeth Blackburn in 1985¹ set the stage for the analysis of this fascinating enzyme. In the...

The Biology of Telomeres in Hypotrichous Ciliates

Franziska Jonsson and Hans J. Lipps

Like other ciliated protozoa, hypotrichous ciliates, to which for example the genera Euplotes, Oxytricha or Stylonychia belong, contain two morphologically and functionally different
types of nuclei in one cell, the diploid micronucleus which...

PNA and Oligonucleotide Inhibitors of Human Telomerase

Gérald Gavory and Shankar Balasubramanian

Telomerase is a ribonucleoprotein enzyme that maintains telomeres; the ends of eukaryotic chromosomes. Human telomerase synthesises TTAGGG tandem repeat sequences at the 3' end of the chromosomes using part of its internal RNA moiety as a template.¹ The discovery that telomera...

Potential of the Telomerase Catalytic Subunit as a Universal Tumor-Associated Antigen for Cancer Immunotherapy

Robert H. Vonderheide and William C. Hahn

Numerous recent studies in both human and animal systems have provided compelling evidence that the immune system can be manipulated to specifically recognize and
kill human tumor cells.¹ Most attention has focused on the CD8⁺ cytotoxic T lymphocyte (CTL)...

RAP1 Binding and Length Regulation of Yeast Telomeres

Johan Wahlin and Marita Cohn

The gene coding for Repressor Activator Protein 1 (RAP1) is essential for S. cerevisiae cellular viability. Since it was first identified some 15 years ago, the RAP1 protein has successively revealed to us that it is a global regulator involved in multiple cel...

Telomeres in Drosophila and Other Insects

Harald Biessmann, Marika F. Walter and James M. Mason

Of the vast numbers of insect species from many orders, only a few have been investigated for telomere structure. However, these studies have revealed the presence of three different types of telomere elongation mechanisms, two of which are also found in other eukaryotes (telomerase and ...

Telomeres and Mechanisms of DNA Double Strand Break Repair

Predrag Slijepcevic

More than half a century ago, the pioneer of radiation genetics, Herman Joseph Muller, proposed that specialized structures, he termed telomeres, must be present at
chromosome ends to protect their stability and integrity.¹ This concept was based on cytological observa...

Amplification of hTERT, the Telomerase Reverse Transcriptase Gene in Human

Dawei Xu, Anju Zhang, Mi Hou, Magnus Björkholm and Astrid Gruber

Telomeres, the nucleoprotein structure consisting of tandemly repeated TTAGGG sequences and associated proteins, form protective caps on human linear chromosome ends, and are essential to maintenance of genomic stability and integrity.^1,2 Telomere DNA is de novo synthesized by...