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

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

Nucleic Acids Res

Telomere Length Regulation Group, Children's Medical Research Institute, Westmead NSW 2145, Australia, Cancer Research Unit, Children's Medical Research Institute, Westmead NSW 2145, Australia, Terry Fox Laboratory, BC Cancer Agency, Vancouver V5Z 1L3, Canada, Sydney Medical School, University of Sydney, Sydney NSW 2006, Australia and Children's Cancer Research Unit, The Children's Hospital at Westmead, Westmead NSW 2145, Australia.

Published: February 2014

AI Article Synopsis

Article Abstract

Telomeres are terminal repetitive DNA sequences on chromosomes, and are considered to comprise almost exclusively hexameric TTAGGG repeats. 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. This indicates that telomerase is most likely an error-prone reverse transcriptase that misincorporates nucleotides at specific positions on the telomerase RNA template. In contrast, cell lines that use the ALT pathway contained a large range of variant repeats that varied greatly between lines. This is consistent with variant repeats spreading from proximal telomeric regions throughout telomeres in a stochastic manner by recombination-mediated templating of DNA synthesis. 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3919612PMC
http://dx.doi.org/10.1093/nar/gkt1117DOI Listing

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