Chapter Category:

From the book Origin and Evolution of Telomeres

Cancer as a Microevolutionary Process Affecting Telomere Structure and Dynamics: The Contribution of Telomeres to Cancer

J. Arturo Londoño-Vallejo

Telomeres play fundamental roles in genome stability, nuclear architecture and chromosome pairing during meiosis. They shorten at every cell division and may be re‑elongated or not depending on the presence of the dedicated enzyme, telomerase. Since in most human somatic cells telomerase is not expressed, shortening of telomeres during development and aging is the rule. Short telomeres being, under physiological conditions, incompatible with extended cell proliferation, telomere length defines the proliferation potential of a cell and operates as a mechanism to prevent uncontrolled cell growth. Conversely, in cells in which proliferation checkpoints have been abolished, shortening of telomeres causes chromosomes to fuse and to initiate cycles of breakage‑fusion‑bridge thus becoming a strong driving force for genome instability. In vitro, transformed cells with highly unstable genomes because of severe telomere shortening accumulate deleterious genetic changes and die (crisis). At the same time, random genetic or epigenetic changes may allow cells to acquire a telomere maintenance mechanism (as well as other tumor phenotypes) and to become immortal. Although telomere shortening and other types of telomere dysfunction probably contribute to the genome instability detected in early tumors in vivo, the direct contributions of dysfunctional telomeres to the acquisition of tumor phenotypes in humans remain largely unspecified.

Taken from the book

Origin and Evolution of Telomeres

Edited by: Jozef Nosek and Ľubomír Tomáska

More chapters from the book:

Telomeric DNA generally comprises a repetitive, noncoding sequence which terminates in a single‑stranded extension, the 3\\\' overhang. Although these species‑specific repeats show a large diversity in sequence and length, they comprise some specific characteristic conserved features....


Linear DNA genomes are sporadically found among viruses, bacteria and organelles. In contrast, virtually all eukaryotic species harbor in their nuclei chromosomes consisting of linear DNA molecules that terminate with specific structures termed telomeres, indicating that this genomic or...


Telomeres play fundamental roles in genome stability, nuclear architecture and chromosome pairing during meiosis. They shorten at every cell division and may be re‑elongated or not depending on the presence of the dedicated enzyme, telomerase. Since in most human somatic cells telomerase is...


In Drosophila, the role of telomerase is carried out by three specialized retrotransposable elements, HeT‑A, TART and Tahre. Telomeres contain long tandem head‑to‑tail arrays of these elements. Within each array, the three elements occur in random, but polarized, order. Some are...


Evolution, Composition and Interrelated Functions of Telomeres and Subtelomeres: Lessons from Plants
Jiří Fajkus, Andrew R. Leitch, Michael Chester and Eva Sýkorová

The terminal parts of chromosomes, telomeres and their subtelomeric neighbors are reviewed. Both have common and specific features that interact to generate the unique and essential biology that characterizes telomeres. The chromatin of both chromosome domains has a nucleosomal structure and...


Telomeres are crucial components required for genomic stability. Telomere dysfunction can result in enormously elevated rates of chromosomal alterations, particularly in subtelomeric regions. Interestingly, the chromosomal regions in the vicinity of telomeres are often among the most rapidly...


Telomerase: Evolution, Structure and Function
Marie-Eve Brault, Yasmin D'Souza and Chantal Autexier

Telomerase is a unique ribonucleoprotein reverse transcriptase that uses an integral RNA template to catalyze the addition of telomeric repeats at telomeres. This mechanism is required for the maintenance of chromosome termini, as the structure and integrity of telomeres are essential for genome...


Alternative Lengthening of Telomeres in Mammalian Cells
Anthony J. Cesare and Roger R. Reddel

For human cells to achieve immortalization they must bypass multiple proliferative checkpoints and acquire a telomere maintenance mechanism to counteract the natural telomere attrition that results from the end‑replication problem. A number of human tumors and cells immortalized in culture...


Prokaryotic Telomeres: Replication Mechanisms and Evolution
Sherwood R. Casjens and Wai Mun Huang

Two types of bacterial telomeres of linear genomes are known. One type involves the covalent attachment of a terminal protein to each of the 5\\\'‑ends and the protective terminal protein is part of the priming complex in new rounds of DNA replication. The second type is a protein free DNA...


Telomere binding proteins provide essential functions for chromosome maintenance in most eukaryotes and consequently are well suited for analysis in the context of evolution. This review focuses on patterns gleaned from structural and functional characterization of telomere proteins that reveal...


T‑Loops, T‑Circles and Slippery Forks
Sarah A. Compton, Anthony J. Cesare, Nicole Fouche, Sezgin Ozgur and Jack D. Griffith

All species with linear chromosomes require telomeres, whose role is to stabilize chromosome ends and prevent undesirable recombination‑mediated or DNA repair‑mediated events involving these DNA ends. The telomeres of most higher eukaryotic species are composed of very long tracts of...


Telomere Position Effect and the Evolution of the Genome
Frederique Magdinier, Alexandre Ottaviani and Eric Gilson

It is now well known that chromatin structure and subnuclear environment play universal roles in the regulation of gene transcription and any type of DNA transactions, including the 3Rs (replication, recombination and repair). Most telomeres and subtelomeres from Saccharomyces cerevisiae to Homo...


Advertisements