Michael Lee, et al., Telomere extension by telomerase and ALT generates variant repeats by mechanistically distinct processes, Nucleic Acids Research, 2014, vol. 42, No. 3, 1733-1746.
We have evaluated telomere sequence content in human cells using whole-genome sequencing followed by telomere read extraction in a panel of mortal cell strains and immortal cell lines. We identified a wide range of telomere variant repeats in human cells, and found evidence that variant repeats are generated by mechanistically distinct processes during telomerase- and ALT-mediated telomere lengthening. Telomerase-mediated telomere extension resulted in biased repeat synthesis of variant repeats that differed from the canonical sequence at positions 1 and 3, but not at positions 2, 4, 5 or 6.
In contrast, cell lines that use the ALT pathway contained a large range of variant repeats that varied greatly between lines.
The presence of unexpectedly large numbers of variant repeats in cells utilizing either telomere maintenance mechanism suggests a conserved role for variant sequences at human telomeres.
We identified a significant increase in GCAGGG variants, specific to the HT1080 hTR TCA cell line.