A genomics approach identifies senescence-specific gene expression regulation

Authors

  • Daniel H. Lackner,

    1. Salk Institute for Biological Studies, Molecular and Cell Biology Laboratory, La Jolla, CA, USA
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  • Makoto T. Hayashi,

    1. Salk Institute for Biological Studies, Molecular and Cell Biology Laboratory, La Jolla, CA, USA
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  • Anthony J. Cesare,

    1. Salk Institute for Biological Studies, Molecular and Cell Biology Laboratory, La Jolla, CA, USA
    Current affiliation:
    1. Children's Medical Research Institute, Genome Integrity Group, Westmead, NSW, Australia
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  • Jan Karlseder

    Corresponding author
    1. Salk Institute for Biological Studies, Molecular and Cell Biology Laboratory, La Jolla, CA, USA
    • Correspondence

      Jan Karlseder, Salk Institute for Biological Studies, Molecular and Cell Biology Laboratory, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA. Tel.: 858 453 4100 x1867; fax: 858 457 4765; e-mail: karlseder@salk.edu

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Summary

Replicative senescence is a fundamental tumor-suppressive mechanism triggered by telomere erosion that results in a permanent cell cycle arrest. To understand the impact of telomere shortening on gene expression, we analyzed the transcriptome of diploid human fibroblasts as they progressed toward and entered into senescence. We distinguished novel transcription regulation due to replicative senescence by comparing senescence-specific expression profiles to profiles from cells arrested by DNA damage or serum starvation. Only a small specific subset of genes was identified that was truly senescence-regulated and changes in gene expression were exacerbated from presenescent to senescent cells. The majority of gene expression regulation in replicative senescence was shown to occur due to telomere shortening, as exogenous telomerase activity reverted most of these changes.

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