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Critical constituents and assembly principles of centriole biogenesis in human cells

Abstract

The centriole is an evolutionarily conserved microtubule-bearing organelle with a striking 9-fold symmetrical architecture that is crucial for fundamental cellular processes in eukaryotes, including polarity, signalling and motility. The last two decades have witnessed important progress in uncovering the molecular architecture and assembly principles governing centriole biogenesis, which are discussed in this Review, with a focus on human cells. Recently developed advanced microscopy approaches have increased our understanding of the mechanisms governing centriole biogenesis, from initiating the assembly process to forming a full-fledged organelle. Some two billion years after its emergence during evolution, and more than 100 years after its identification by pioneering scientists, these advances make the centriole ripe for another era of discoveries.

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Fig. 1: The roots of centriole biology.
Fig. 2: Centriole architecture.
Fig. 3: Mentored centriole duplication cycle.
Fig. 4: Modules operating sequentially during the centriole duplication cycle.

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Acknowledgements

The author is grateful to G. N. Hatzopoulos for help preparing most figure panels, and thanks F. Douma for Fig. 1b as well as P. Keeling for generating a Creative Commons version of the figure for Supplementary Box 1 that could be adapted here. Moreover, G. N. Hatzopoulos, F. Douma and S. Aich are acknowledged for their useful comments on the manuscript. The author apologizes to those scientists whose work could not be mentioned due to space limitations or ignorance. Work on centriole assembly in the author’s laboratory during writing of this review was supported by the European Research Council (AdG 588437) and Swiss Cancer Research (KFS-6018-02-2024-R).

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Correspondence to Pierre Gönczy.

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Nature Reviews Molecular Cell Biology thanks Mónica Bettencourt-Dias, Fanny Gergely and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Glossary

APC/C

(anaphase-promoting complex, also known as the cyclosome). A large protein complex with E3 ubiquitin ligase activity that poly-ubiquitinates target cell cycle proteins, thus marking them for degradation by the 26S proteasome.

Axoneme

A microtubule-based structure in cilia and flagella that exhibits a 9-fold radial symmetry of microtubule doublets stemming from the likewise symmetrical centriolar microtubule doublets.

Cryo electron tomography

(cryo-ET). Electron microscopy approach in which the specimen is preserved in the native state by freezing at cryogenic temperature, and then imaged through a tilt series, followed by specimen reconstruction.

Dynamic instability

Refers to the ensemble dynamic behaviour of microtubules: once nucleated, microtubules switch between growth and shrinkage phases at their plus end, with catastrophe and rescue events between the two phases.

G1/S transition

A cell cycle transition between the G1 phase that follows mitosis and the S phase, when DNA replication takes place; the G1/S transition generally commits the cell to completing the cell cycle.

Pericentriolar material

(PCM). A region surrounding centrioles from where most microtubules are nucleated in many animal cells.

Ultrastructural expansion microscopy

(U-ExM). A method in which the specimen is augmented isotropically using a swellable hydrogel, thereby enlarging the effective resolution correspondingly.

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Gönczy, P. Critical constituents and assembly principles of centriole biogenesis in human cells. Nat Rev Mol Cell Biol 27, 260–277 (2026). https://doi.org/10.1038/s41580-025-00921-5

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