Review Article

Once and only once: mechanisms of centriole duplication and their deregulation in disease

  • Nature Reviews Molecular Cell Biology volume 19, pages 297312 (2018)
  • doi:10.1038/nrm.2017.127
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Abstract

Centrioles are conserved microtubule-based organelles that form the core of the centrosome and act as templates for the formation of cilia and flagella. Centrioles have important roles in most microtubule-related processes, including motility, cell division and cell signalling. To coordinate these diverse cellular processes, centriole number must be tightly controlled. In cycling cells, one new centriole is formed next to each pre-existing centriole in every cell cycle. Advances in imaging, proteomics, structural biology and genome editing have revealed new insights into centriole biogenesis, how centriole numbers are controlled and how alterations in these processes contribute to diseases such as cancer and neurodevelopmental disorders. Moreover, recent work has uncovered the existence of surveillance pathways that limit the proliferation of cells with numerical centriole aberrations. Owing to this progress, we now have a better understanding of the molecular mechanisms governing centriole biogenesis, opening up new possibilities for targeting these pathways in the context of human disease.

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Acknowledgements

The authors thank their laboratory members for helpful discussions and apologize to colleagues whose work could not be cited due to space limitations. Work in the authors' laboratories was supported by grants from the Swiss National Science Foundation (310030B-149641) to E.A.N. and a R01 research grant from the US National Institutes of Health (GM 114119), an American Cancer Society Scholar Grant (129742-RSG-16-156-01-CCG) and a March of Dimes Research Grant (1-FY17-698) to A.J.H.

Author information

Affiliations

  1. Biozentrum, University of Basel, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland.

    • Erich A. Nigg
  2. Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.

    • Andrew J. Holland

Authors

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  2. Search for Andrew J. Holland in:

Contributions

Both E.A.N. and A.J.H. researched data for the article, made substantial contributions to the discussion of content, wrote the article, and reviewed and edited the manuscript before submission.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Erich A. Nigg or Andrew J. Holland.

Glossary

Procentriole

A newly constructed centriole that is unable to duplicate.

A tubules

A typical microtubule triplet is composed of A, B and C tubules, with the innermost A tubule being built from 13 protofilaments.

Molecular rulers

Molecules of defined size that can be used to set distances between other structures.

Axoneme

The nine-fold symmetrical microtubule-based structure at the centre of cilia and flagella.

WD40 protein

A structural motif of approximately 40 amino acids, often terminating in a tryptophan-aspartic acid (WD) dipeptide.

Planarians

Flatworms used as a model system to study regeneration.

Hippo pathway

A signalling pathway that controls organ size in animals by restraining cell proliferation and promoting apoptosis.

PIDDosome

A protein complex composed of death domain-containing protein CRADD (also known as RAIDD) and p53-induced death domain-containing protein 1 (PIDD1) that is implicated in the activation of caspase 2.

Cytokinesis failure

Failure to physically separate the two daughter cells after chromosome segregation is completed.

Neuroblasts

Dividing neuronal precursor cells.

Aneuploidy

The presence of an abnormal chromosome number that is not a multiple of the haploid chromosome complement.

Merotelic attachments

Spindle microtubule–chromosome attachments in which one kinetochore binds microtubules emanating from two centrosomes located on opposite sides of the mitotic spindle.

Micronuclei

Small nuclei that are separate from the cell nucleus and that contain one or a few chromosomes or chromosome fragments.

RAC1

A small GTPase member of the RAS superfamily with diverse cellular functions.

Organoids

An in vitro culture system that mimics the micro-anatomy of an organ.

Hypomorphic mutations

Mutations that cause a partial loss of gene function.