Senescent Cells Harbour Features of the Cancer Epigenome

Hazel A. Cruickshanks, Tony McBryan, David M. Nelson, Nathan D. Vanderkraats, Parisha P. Shah, John Van Tuyn, Taranjit Singh Rai, Claire Brock, Greg Donahue, Donncha S. Dunican, Mark E. Drotar, Richard R. Meehan, John R. Edwards, Shelley L. Berger, Peter D. Adams

Research output: Contribution to journalArticle

133 Citations (Scopus)

Abstract

Altered DNA methylation and associated destabilization of genome integrity and function is a hallmark of cancer. Replicative senescence is a tumour suppressor process that imposes a limit on the proliferative potential of normal cells that all cancer cells must bypass. Here we show by whole-genome single-nucleotide bisulfite sequencing that replicative senescent human cells exhibit widespread DNA hypomethylation and focal hypermethylation. Hypomethylation occurs preferentially at gene-poor, late-replicating, lamin-associated domains and is linked to mislocalization of the maintenance DNA methyltransferase (DNMT1) in cells approaching senescence. Low-level gains of methylation are enriched in CpG islands, including at genes whose methylation and silencing is thought to promote cancer. Gains and losses of methylation in replicative senescence are thus qualitatively similar to those in cancer, and this ‘reprogrammed’ methylation landscape is largely retained when cells bypass senescence. Consequently, the DNA methylome of senescent cells might promote malignancy, if these cells escape the proliferative barrier.

LanguageEnglish
Pages1495-1506
Number of pages12
JournalNature Cell Biology
Volume15
Issue number12
DOIs
Publication statusPublished - 1 Jan 2013

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Cell Aging
Methylation
Neoplasms
DNA
Genome
Lamins
CpG Islands
Methyltransferases
DNA Methylation
Genes
Nucleotides
Maintenance

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Cruickshanks, H. A., McBryan, T., Nelson, D. M., Vanderkraats, N. D., Shah, P. P., Van Tuyn, J., ... Adams, P. D. (2013). Senescent Cells Harbour Features of the Cancer Epigenome. Nature Cell Biology, 15(12), 1495-1506. https://doi.org/10.1038/ncb2879
Cruickshanks, Hazel A. ; McBryan, Tony ; Nelson, David M. ; Vanderkraats, Nathan D. ; Shah, Parisha P. ; Van Tuyn, John ; Singh Rai, Taranjit ; Brock, Claire ; Donahue, Greg ; Dunican, Donncha S. ; Drotar, Mark E. ; Meehan, Richard R. ; Edwards, John R. ; Berger, Shelley L. ; Adams, Peter D. / Senescent Cells Harbour Features of the Cancer Epigenome. In: Nature Cell Biology. 2013 ; Vol. 15, No. 12. pp. 1495-1506.
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Cruickshanks, HA, McBryan, T, Nelson, DM, Vanderkraats, ND, Shah, PP, Van Tuyn, J, Singh Rai, T, Brock, C, Donahue, G, Dunican, DS, Drotar, ME, Meehan, RR, Edwards, JR, Berger, SL & Adams, PD 2013, 'Senescent Cells Harbour Features of the Cancer Epigenome', Nature Cell Biology, vol. 15, no. 12, pp. 1495-1506. https://doi.org/10.1038/ncb2879

Senescent Cells Harbour Features of the Cancer Epigenome. / Cruickshanks, Hazel A.; McBryan, Tony; Nelson, David M.; Vanderkraats, Nathan D.; Shah, Parisha P.; Van Tuyn, John; Singh Rai, Taranjit; Brock, Claire; Donahue, Greg; Dunican, Donncha S.; Drotar, Mark E.; Meehan, Richard R.; Edwards, John R.; Berger, Shelley L.; Adams, Peter D.

In: Nature Cell Biology, Vol. 15, No. 12, 01.01.2013, p. 1495-1506.

Research output: Contribution to journalArticle

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Cruickshanks HA, McBryan T, Nelson DM, Vanderkraats ND, Shah PP, Van Tuyn J et al. Senescent Cells Harbour Features of the Cancer Epigenome. Nature Cell Biology. 2013 Jan 1;15(12):1495-1506. https://doi.org/10.1038/ncb2879