Chapter category:

T‑Loops, T‑Circles and Slippery Forks

This chapter appears in the following book:

Origin and Evolution of Telomeres

Edited by: Jozef Nosek and Ľubomír Tomáska
ISBN: 978-1-58706-309-1
» Get more information about this book at landesbioscience.com «

Chapter authors:
Sarah A. Compton, Anthony J. Cesare, Nicole Fouche, Sezgin Ozgur and Jack D. Griffith

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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 a short repeated DNA sequence that is G‑rich on one strand. These tracts are variable in length, ranging from approximately 3 kb in Arabidopsis, 15 to 50 kb in some rodents, to 100 kb or longer in some plants such as garden peas and tobacco. Telomeric DNA interacts with histones and other chromatin proteins to form chromatin, which in turn forms a higher order looped structure called a t‑loop. Under some circumstances, t‑loops may be converted to or generate extrachromosomal t‑circles; for example, t‑circles are associated with the Alternative Lengthening of Telomeres (ALT) pathway, which maintains telomere length by a telomerase‑independent recombination‑dependent mechanism. Recent studies show that formation of t‑circles in human ALT cells is dependent on several recombination proteins. Telomeric DNA faces unusual impediments to replication; in particular, the replication fork has a tendency to stall in tracts of short DNA repeats. To facilitate replication of telomeric repeats, the replication fork may interact with telomere‑specific factors, such as TRF2, which may prevent replication fork slippage. While telomeric DNA has several unique properties and is compacted differently from euchromatic DNA, telomeric DNA may share some traits and behaviors with other tracts of short repeats such as the triplet repeats associated with Huntington disease, Fragile X syndrome and Myotonic Dystrophy. Thus, studies of telomeric DNA may yield insight into mechanisms involved in triplet repeat expansion. This chapter reviews recent insights into unique structural elements of telomeres including t‑loops and t‑circles and discusses possible relationships between telomere biology and human triplet diseases.

Sarah A. Compton
Lineberger Comprehensive Cancer Center

Anthony J. Cesare
Children's Medical Research Institute

Nicole Fouche
Lineberger Comprehensive Cancer Center

Sezgin Ozgur
Lineberger Comprehensive Cancer Center

Jack D. Griffith
Lineberger Comprehensive Cancer Center, University of North Carolina

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T‑Loops, T‑Circles and Slippery Forks

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