Telomere extension by telomerase and ALT generates variant repeats by mechanistically distinct processes

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.

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