Telomeric circles: universal players in telomere maintenance? - PubMed (original) (raw)

. 2009 Oct;16(10):1010-5.

doi: 10.1038/nsmb.1660. Epub 2009 Oct 6.

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Telomeric circles: universal players in telomere maintenance?

Lubomir Tomaska et al. Nat Struct Mol Biol. 2009 Oct.

Abstract

To maintain linear DNA genomes, organisms have evolved numerous means of solving problems associated with DNA ends (telomeres), including telomere-associated retrotransposons, palindromes, hairpins, covalently bound proteins and the addition of arrays of simple DNA repeats. Telomeric arrays can be maintained through various mechanisms such as telomerase activity or recombination. The recombination-dependent maintenance pathways may include telomeric loops (t-loops) and telomeric circles (t-circles). The potential involvement of t-circles in telomere maintenance was first proposed for linear mitochondrial genomes. The occurrence of t-circles in a wide range of organisms, spanning yeasts, plants and animals, suggests the involvement of t-circles in many phenomena including the alternative-lengthening of telomeres (ALT) pathway and telomere rapid deletion (TRD). In this Perspective, we summarize these findings and discuss how t-circles may be related to t-loops and how t-circles may have initiated the evolution of telomeres.

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Figures

Figure 1

Figure 1

t-circles and t-loops seem to be common players in telomere maintenance. (a) Proposed pathway in the maintenance of mitochondrial telomeres in the yeast C. parapsilosis. The mitochondrial telomeres consist of t-arrays (n × 738 bp) with a 5′ single-stranded overhang of about 110 nt. Invasion of the overhang into the double-stranded region of t-arrays can form t-loop structures. The t-circles can be formed either by intramolecular recombination between repeats within t-arrays or by excision from t-loops. The t-circles amplify autonomously via a rolling-circle mechanism (forming σ-form ‘tailed circles’), thus generating long extrachromosomal t-arrays, which can recombine with the main genome and extend the termini. EM revealed the key players in the proposed pathway of the mitochondrial telomere maintenance,,,,. (b) Proposed role for the rolling-circle synthesis in nuclear telomere maintenance. Rolling-circle synthesis can extend the termini in situ (on a t-loop or single-stranded or double-stranded t-circles), or extrachromosomal t-circles may replicate autonomously.

Figure 2

Figure 2

Evolutionary scenario for the emergence of linear chromosomes terminating with t-arrays and hypotheses on the emergence of t-circles. (a) Genome rearrangements within a circular genome may result in formation of a palindrome. Alternatively, a selfish genetic element may ‘infect’ a circular genome. Subsequent resolution of the palindrome eventually generates a linear molecule with t-hairpins at the ends. The termini represent a substrate for recombination with t-circles and/or elongation by telomerase. Expanded t-arrays allow the formation of higher-order structures such as t-loops and the emergence of telomere maintenance mechanism(s). We have proposed three mechanisms that may explain the emergence of t-circles. (b) Similarities between mitochondrial t-circles and hypersuppresive (ρ −) petite genomes indicate that they could have emerged by a common mechanism. Hypersuppressive genomes represent short fragments of a mitochondrial genome, which replicates via rolling-circle synthesis. In baker’s yeast, hypersuppressive genomes can outcompete the main genome. However, in strictly aerobic _petite_-negative organisms, the two replicons (mtDNA and hypersuppressive-like t-circles) can coexist, and eventually the t-circles can recombine with mtDNA, which may result in the formation of a linear DNA genome with t-arrays at the ends. Rolling-circle replicating t-circles may escape from the mitochondria to the nucleus and analogously affect the nuclear genome. (c) Alternatively, t-circles may emerge from intra-strand recombination of units within a preexisting intrachromosomal array of tandem repeats. (d) T-circles may also emerge by reverse transcription of an RNA molecule (or an RNA fragment, shown in gray), which serves as a template for the first-strand cDNA synthesis, followed by template degradation, synthesis of the second cDNA strand and ligation of nicks. The double-stranded DNA circle is either discarded (most cases) because of its inability to replicate, or if it is able to replicate it can be preserved and may invade into the main genome or chromosome, as shown in a.

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References

    1. Gilson E, Géli V. How telomeres are replicated. Nat Rev Mol Cell Biol. 2007;8:825–838. - PubMed
    1. McEachern MJ, Krauskopf A, Blackburn EH. Telomeres and their control. Annu Rev Genet. 2000;34:331–358. - PubMed
    1. Verdun RE, Karlseder J. Replication and protection of telomeres. Nature. 2007;447:924–931. - PubMed
    1. Nosek J, Kosa P, Tomaska L. On the origin of telomeres: a glimpse at the pre-telomerase world. Bioessays. 2006;28:182–190. - PubMed
    1. Pardue ML, DeBaryshe PG. Drosophila telomeres: a variation on the telomerase theme. In: Nosek J, Tomaska L, editors. Origin and Evolution of Telomeres. Landes Bioscience; Austin, Texas: 2008. pp. 27–44. - PubMed

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