Senescent cells harbour features of the cancer epigenome

Cruickshanks, H.A. et al. (2013) Senescent cells harbour features of the cancer epigenome. Nature Cell Biology, 15(12), pp. 1495-1506. (doi: 10.1038/ncb2879)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Rai, Dr Taranjit and Nelson, Mr David and Reid, Mrs Claire and Cruickshanks, Dr Hazel and Drotar, Mr Mark and Adams, Professor Peter and van Tuyn, Dr John and McBryan, Dr Anthony
• Authors: Cruickshanks, H.A., McBryan, A., Nelson, D.M., VanderKraats, N.D., Shah, P.P., van Tuyn, J., Rai, T.S., Brock, C., Donahue, G., Dunican, D.S., Drotar, M.E., Meehan, R.R., Edwards, J.R., Berger, S.L., and Adams, P.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Nature Cell Biology
• ISSN: 1465-7392
• ISSN (Online): 1476-4679