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Molecular basis of telomere dysfunction in human genetic diseases

Nature Structural & Molecular Biology volume 22, pages 867–874 (2015)Cite this article

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An Erratum to this article was published on 06 June 2017

This article has been updated

Abstract

Mutations in genes encoding proteins required for telomere structure, replication, repair and length maintenance are associated with several debilitating human genetic disorders. These complex telomere biology disorders (TBDs) give rise to critically short telomeres that affect the homeostasis of multiple organs. Furthermore, genome instability is often a hallmark of telomere syndromes, which are associated with increased cancer risk. Here, we summarize the molecular causes and cellular consequences of disease-causing mutations associated with telomere dysfunction.

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Figure 1: Role of telomerase in telomere replication.
Figure 2: Shelterin protein complex.
Figure 3: Human telomerase holoenzyme and telomerase accessory proteins.
Figure 4: Schematic view of telomerase trafficking.

Change history

  • 20 April 2017

    The schematic of the TERT subunit in Figure 1 incorrectly identified the 'Internal RNA template': it now correctly indicates the telomerase RNA. The RNA template sequence has been corrected from AAUCCCAAU to AAUCCCAAUC, and the DNA sequence of the repeat synthesis product added to the 3′ overhang was changed from GGGTTA to GGTTAG.

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Acknowledgements

Research in the DNA damage–response laboratory of S.J.B. is funded by The Francis Crick Institute, a European Research Council (ERC) Advanced Investigator Grant (RecMitMei) and a Senior Investigator grant from the Wellcome Trust. S.J.B. is supported as a recipient of a Royal Society Wolfson Research Merit Award. G.S. is funded by an European Molecular Biology Organization (EMBO) Advanced Fellowship. P. Marzec and P. Margalef are funded by EMBO long-term fellowships.

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  1. Grzegorz Sarek, Paulina Marzec and Pol Margalef: These authors contributed equally to this work.

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  1. DNA Damage Response Laboratory, Francis Crick Institute, South Mimms, UK

    Grzegorz Sarek, Paulina Marzec, Pol Margalef & Simon J Boulton

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  1. Grzegorz Sarek
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Sarek, G., Marzec, P., Margalef, P. et al. Molecular basis of telomere dysfunction in human genetic diseases. Nat Struct Mol Biol 22, 867–874 (2015). https://doi.org/10.1038/nsmb.3093

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