ATM Kinase Is Required for Telomere Elongation in Mouse and Human Cells

Stella Suyong Lee, Craig Bohrson, Alexandra Mims Pike, Sarah Jo Wheelan, Carol Widney Greider

Research output: Contribution to journalArticlepeer-review

Abstract

Short telomeres induce a DNA damage response, senescence, and apoptosis, thus maintaining telomere length equilibrium is essential for cell viability. Telomerase addition of telomere repeats is tightly regulated in cells. To probe pathways that regulate telomere addition, we developed the ADDIT assay to measure new telomere addition at a single telomere in vivo. Sequence analysis showed telomerase-specific addition of repeats onto a new telomere occurred in just 48 hr. Using the ADDIT assay, we found that ATM is required for addition of new repeats onto telomeres in mouse cells. Evaluation of bulk telomeres, in both human and mouse cells, showed that blocking ATM inhibited telomere elongation. Finally, the activation of ATM through the inhibition of PARP1 resulted in increased telomere elongation, supporting the central role of the ATM pathway in regulating telomere addition. Understanding this role of ATM may yield new areas for possible therapeutic intervention in telomere-mediated disease.

Original languageEnglish (US)
Pages (from-to)1623-1632
Number of pages10
JournalCell Reports
Volume13
Issue number8
DOIs
StatePublished - Nov 24 2015

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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