Abstract
Tandem DNA repeats derived from the ancestral (TTAGGG)n run were first detected at chromosome ends of the majority of living organisms, hence the name telomeric DNA repeats. Subsequently, it has become clear that telomeric motifs are also present within chromosomes, and they were suitably called interstitial telomeric sequences (ITSs). It is well known that telomeric DNA repeats play a key role in chromosome stability, preventing end-to-end fusions and precluding the recurrent DNA loss during replication. Recent data suggest that ITSs are also important genomic elements as they confer its karyotype plasticity. In fact, ITSs appeared to be among the most unstable microsatellite sequences as they are highly length polymorphic and can trigger chromosomal fragility and gross chromosomal rearrangements. Importantly, mechanisms responsible for their instability appear to be similar to the mechanisms that maintain the length of genuine telomeres. This review compares the mechanisms of maintenance and dynamic properties of telomeric repeats and ITSs and discusses the implications of these dynamics on genome stability.
Highlights
Tandem DNA repeats derived from the ancestral (TTAGGG)n run were first detected at chromosome ends of the majority of living organisms, the name telomeric DNA repeats
We suggest that binding of multiple Rap1 molecules to the interstitial yeast telomeric (Ytel) repeat creates a polar block for the replication machinery, which can result in either fork collapse or a modest fork slowing, depending on the repeat’s orientation
interstitial telomeric sequences (ITSs) have been viewed for a long time as a junk DNA associated with chromosomal rearrangements and aberrations
Summary
The ends of chromosomes, called telomeres, are natural protective caps that perform two important functions: they prevent chromosomes from end-to-end fusions and from their fusion to accidental double-strand breaks (DSBs) [1,2,3,4] and preclude recurrent DNA loss occurring during replication [5,6,7]. Telomeric repeats may be regular (such as TTAGGG in humans and most vertebrates or TTGGGG in Tetrahymena) or irregular (such as G1–3 T in yeast Saccharomyces cerevisiae), and their actual copy number at the end of chromosome may vary from as few as 2–3 repeats in hypotrichous ciliates, such as Oxytricha, to thousands of copies in mammals and the total length of a telomere can reach more than 100 kb in mice and up to 2 Mb in chicken [10,16]. One of the DNA strands of telomeric repeats is enriched in G residues This strand runs 5’→3’ toward the chromosome end and it is longer than its C-rich counterpart, forming a 3’-overhang at the end of a chromosome. Budding yeast’s telomeres are very short and are composed of irregular repeats with a double-stranded region of on average 300±75 bp and a short single-stranded G-rich overhang whose length is maintained around 12–15 nt throughout most of the cell cycle, significantly longer. This mechanism could result from the accumulation of telomeric retrotransposons that target TTAGG and variant TCAGG repeats in a sequence-specific manner [26,27]
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