Subtelomeric

Subtelomeres are segments of DNA between telomeric caps and chromatin.

Telomeres are specialized protein–DNA constructs present at the ends of eukaryotic chromosomes, which prevent them from degradation and end-to-end chromosomal fusion. Introductory biology courses often describe telomeres as a type of chromosomal aglet. Most vertebrate telomeric DNA consists of long (TTAGGG)n repeats of variable length, often around 3-20kb. Subtelomeres are segments of DNA between telomeric caps and chromatin. Each chromosome has two subtelomeres immediately adjacent to the long (TTAGGG)n repeats. Subtelomeres are considered to be the most distal (farthest from the centromere) region of unique DNA on a chromosome and they are unusually dynamic and variable mosaics of multichromosomal blocks of sequence. The subtelomeres of such diverse species as Humans, Plasmodium falciparum, Drosophila melanogaster or Saccharomyces cerevisiae, are structurally similar in that they are composed of various repeated elements, but the extent of the subtelomeres and the sequence of the elements vary greatly among organisms. In yeast (S. cerevisiae), subtelomeres are composed of two domains : the proximal and distal (telomeric) domains. The two domains differ in sequence content and extent of homology to other chromosome ends and they are often separated by a stretch of degenerate telomere repeats (TTAGGG) and an element called 'core X', which is found at all chromosome ends and contains an autonomously replicating sequence (ARS) and an ABF1 binding site. The proximal domain is composed of variable interchromosomal duplications (<1-30 kb), this region can contain genes such Pho, Mel, Mal and open reading frames (ORFs). The distal domain is composed of 0-4 tandem copies of the highly conserved Y' element which contains other ORFs, the number and chromosomal distribution of Y′ elements varies among yeast strains. Between the core X and the Y' element or the core X and TTAGGG sequence there is often a set of 4 'subtelomeric repeats elements' (STR) : STR-A, STR-B, STR-C and STR-D which consists of multiple copies of the vertebrate telomeric motif TTAGGG. This two-domain structure is remarkably similar to the subtelomere structure in human chromosomes 20p, 4q and 18p in which proximal and distal subtelomeric domains are separated by a stretch of degenerate TTAGGG repeats, but, the picture that emerges from studies of the subtelomeres of other human chromosomes indicates that the two-domain model does not apply universally.

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