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T-loops and the origin of telomeres

Nature Reviews Molecular Cell Biology volume 5, pages 323–329 (2004)Cite this article

An Addendum to this article was published on 01 June 2004

Abstract

Most eukaryotes stabilize the ends of their linear chromosomes with a telomerase-based system. Telomerase maintains specific repetitive sequences, which protect chromosome ends with the help of telomere-binding proteins. How did this elaborate system evolve? Here, I propose that telomere function was originally mediated by t-loops, which could have been generated by prokaryotic DNA-replication factors. These early telomeres would have required only the presence of a few repeats at chromosome ends. Telomerase could have been a later innovation with specific advantages for telomere function and regulation.

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Figure 1: Solutions to the end-replication problem.
Figure 2: Proposed structure of the human telomeric complex.
Figure 3: T-loop formation resembles initiation of RDR.
Figure 4: The t-loop-evolution model.

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Acknowledgements

I dedicate this article to the memory of Anat Krauskopf. K. Kreuzer, J. Haber, V. Lundblad, R. Reddel, K. Hoke, and S. Buonomo provided extremely helpful criticism of these ideas. I thank J. Griffith for comments on this manuscript and for long-term collaborative efforts on t-loops. B. Bowerman is acknowledged for sage advice ('Evolution happened. Get over it.'). Space limitations prevented me from providing a thorough review of all relevant publications and I refer to the cited reviews for many important primary references. Research on telomeres in my laboratory is funded by the National Institutes of Health, the National Cancer Institute and the Ellison Foundation.

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  1. the Laboratory for Cell Biology and Genetics, Box 159, The Rockefeller University, 1230 York Avenue, New York, 10021, New York, USA

    Titia de Lange

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DATABASES

Entrez

RecA

SSB

Flybase

HetA

TART

OMIM

Bloom syndrome

Werner syndrome

Saccharomyces genome database

Cdc13

Mre11

Rad50

Rad51

Xrs2

Schizosaccharomyces pombe gene database

Taz1

Pot1

Swiss-Prot

BLM

NBS1

RAD54

TRF2

WRN

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de Lange, T. T-loops and the origin of telomeres. Nat Rev Mol Cell Biol 5, 323–329 (2004). https://doi.org/10.1038/nrm1359

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