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DNA repair

Telomere-lengthening mechanism revealed

Nature volume 539, pages 35–36 (2016)Cite this article

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Shortening of the ends of chromosomes limits a cell's lifespan. Some cancer cells avoid this fate through a mechanism called alternative lengthening of telomeres, molecular details of which have now been defined. See Article p.54

During cell division, the genome is duplicated by DNA polymerase enzymes. However, each chromosome's ends are incompletely replicated during duplication, because DNA polymerases require an RNA primer 5′ to the region being synthesized. This means that the repetitive DNA sequences called telomeres that cap the ends of chromosomes shorten at each division, and this shortening limits the replicative lifespans of most cells. During cancer development, cells acquire the ability to divide indefinitely by circumventing telomere shortening — either by upregulating the enzyme telomerase, which extends telomeres, or by activating a mechanism termed alternative lengthening of telomeres (ALT), which is based on a common method of DNA repair, homologous recombination. On page 54, Dilley et al.1 reveal a mechanism that underlies ALT and identify an unusual DNA polymerase that mediates this process.

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Figure 1: Break-induced telomere synthesis.

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Authors and Affiliations

  1. Caitlin M. Roake and Steven E. Artandi are in the Departments of Medicine and of Biochemistry and the Cancer Biology Program, Stanford University School of Medicine, Stanford, California 94305, USA.,

    Caitlin M. Roake & Steven E. Artandi

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  1. Caitlin M. Roake
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  2. Steven E. Artandi
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Correspondence to Steven E. Artandi.

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Roake, C., Artandi, S. Telomere-lengthening mechanism revealed. Nature 539, 35–36 (2016). https://doi.org/10.1038/nature19483

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