Variant repeats are interspersed throughout the telomeres and recruit nuclear receptors in ALT cells

Dimitri Conomos, et al., Variant repeats are interspersed throughout the telomeres and recruit nuclear receptors in ALT cells, J. Cell Biol. 199, 2012

Telomeres in cells that use recombination-mediated alternative lengthening of telomeres (ALT) pathway elicit a DNA damage response that is partly independent of telomere length.

Here we used next generation sequencing to analyze the DNA content of ALT telomeres. We discovered that variant repeats were interspersed throughout the telomeres of ALT cells. We found that the C-type (TCAGGG) variant repeat predominated and created a high-affinity binding site for the nuclear receptors COUP-TF2 and TR4.

We used next generation sequencing to quantitatively determine the identity and extent of variant sequence within telomere arrays of WI38-VA13/2RA as well as the telomerase-positive HeLa cell line. Samples were paired-end sequenced, and reads containing greater than six nonconsecutive telomeric repeats in the format TBAGGG were considered to be reads derived from telomeres.

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