Volume 522 Issue 7557, 25 June 2015

An adapted image showing condensed mitotic chromosomes (blue); co-localization between telomeric TTAGGG repeats (green) and a DNA damage marker (red) indicates that telomeres are recognized as damage in cells that spontaneously arrest in mitosis during crisis. Cells forming a tumour must overcome two barriers before becoming cancerous. The first is senescence and the second is a proliferative block known as crisis. Cells that escape senescence usually succumb during crisis, but it has not been clear what triggers cell death at that stage. Jan Karlseder and colleagues now demonstrate that cells that bypass senescence in the absence of p53 have shortened telomeres that undergo fusion, and these fusions trigger mitotic delay. During mitotic arrest telomeres are further deprotected and detected by the DNA damage machinery, which leads to cell death. These findings might offer a clinical opportunity, as exacerbation of mitotic telomere deprotection sensitizes cancer cells to mitotic drugs � but mitotic arrest has also been associated with genome instability and tumorigenesis in checkpoint-compromised cells. (Cover illustration by Jamie Simon, The Salk Institute)

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Corrections

Nature Outlook

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