Amplification of telomeric arrays via rolling-circle mechanism.
Nosek J, Rycovska A, Makhov AM, Griffith JD, Tomaska L
Journal of Biological Chemistry (2005)
Category: mitochondrial DNA, telomere ¤ Added: Mar 14, 2005 ¤ Rating: ◊◊
Alternative (telomerase-independent) lengthening of telomeres mediated through homologous recombination is often accompanied by a generation of extrachromosomal telomeric circles (t-circles), whose role in direct promotion of recombinational telomere elongation has been recently demonstrated. Here we present evidence that t-circles in a natural telomerase-deficient system of mitochondria of the yeast Candida parapsilosis replicate independently of the linear chromosome via a rolling-circle mechanism. This is supported by an observation of (i) single-stranded DNA (ssDNA) consisting of concatemeric arrays of telomeric sequence, (ii) lasso-shaped molecules representing rolling-circle intermediates, and (iii) preferential incorporation of deoxyribonucleotides into telomeric fragments and t-circles. Analysis of naturally occurring variant t-circles revealed conserved motifs with potential function in driving the rolling-circle replication. This data indicates that extrachromosomal t-circles observed in a wide variety of organisms including yeasts, plants, Xenopus laevis, and certain human cell lines may represent independent replicons generating telomeric sequences and thus actively participating in telomere dynamics. Moreover, due to the promiscuous occurrence of t-circles across phyla, the results from yeast mitochondria have implications related to the primordial system of telomere maintenance providing a paradigm for evolution of telomeres in nuclei of early eukaryotes.