Loss of centrioles causes chromosomal instability in vertebrate somatic cells

Sir, Joo-Hee; Pütz, Monika; Daly, Owen; Morrison, Ciarán; Dunning, Mark J.; Kilmartin, John V.; Gergely, Fanni

doi:10.1083/jcb.201309038

Cited by 118 publications

(125 citation statements)

References 53 publications

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“…Many studies have correlated centrosomal aberrations with abnormal spindles and chromosomal instability (17,(40)(41)(42). Staining for α-tubulin in Sas4 −/− p53 −/− MEFs showed that bipolar spindles formed in the absence of SAS4 (Fig.…”

Section: Sas4-nullmentioning

confidence: 92%

“…Abnormal numbers of centrioles are associated with cancer, although it is not clear whether abnormal centrosome number is a cause or an effect of tumorigenesis (1,(11)(12)(13). Studies in cultured cell lines have given conflicting results on the roles of vertebrate centrioles in mitosis, chromosome segregation, DNA damage response, and intercellular signaling (14)(15)(16)(17)(18)(19), but the precise functions of mammalian centrioles have not been defined genetically.…”

mentioning

confidence: 99%

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Acentriolar mitosis activates a p53-dependent apoptosis pathway in the mouse embryo

Bazzi

Anderson

2014

Proc. Natl. Acad. Sci. U.S.A.

177

201

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Significance Centrioles form the core of centrosomes, which organize cilia and interphase and spindle microtubules in animal cells, but centrosome function has not been defined in mammals in vivo. We show that mouse embryos that lack centrioles and centrosomes survive to midgestation, when they lack primary cilia and cilia-dependent signaling. Despite the absence of centrosomes, bipolar spindle formation, chromosome segregation, cell-cycle profile, and DNA damage response are normal in the mutants. Unlike mutants that lack cilia, most cells in acentriolar embryos activate a p53-dependent apoptotic pathway. The data show that mammalian centrioles promote the efficient and rapid assembly of the mitotic spindle and that a short delay in prometaphase activates a checkpoint that leads to p53-dependent cell death in vivo.

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Section: Sas4-nullmentioning

confidence: 92%

mentioning

confidence: 99%

Acentriolar mitosis activates a p53-dependent apoptosis pathway in the mouse embryo

Bazzi

Anderson

2014

Proc. Natl. Acad. Sci. U.S.A.

177

201

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“…Loss of centrosome integrity in cultured cells has been reported to induce senescence or p38 mitogen-activated protein kinase-dependent G1 arrest but whether these occur in cells with MCPH mutations remains to be seen [48][49][50]. Cells with abnormal centrosome numbers take longer to form a bipolar spindle and consequently show a mitotic delay [51][52][53][54][55]. In fact, mitotic delay is the major phenotype seen after depletion of WDR62, ASPM and STIL in developing zebrafish retinal neuroepithelium [56].…”

Section: Centrosomes In Brain Developmentmentioning

confidence: 99%

“…Cells containing too few or too many centrosomes exhibit transient anastral, mono-or multipolar spindles and frequent chromosome missegregation [53,61,62]. Chromosomal instability generates aneuploidy, which has a strong anti-proliferative effect owing to imbalanced gene expression [63].…”

Section: Centrosomes In Brain Developmentmentioning

confidence: 99%

Small organelle, big responsibility: the role of centrosomes in development and disease

Chavali

Pütz

Gergely

2014

Phil. Trans. R. Soc. B

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140

111

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The centrosome, a key microtubule organizing centre, is composed of centrioles, embedded in a protein-rich matrix. Centrosomes control the internal spatial organization of somatic cells, and as such contribute to cell division, cell polarity and migration. Upon exiting the cell cycle, most cell types in the human body convert their centrioles into basal bodies, which drive the assembly of primary cilia, involved in sensing and signal transduction at the cell surface. Centrosomal genes are targeted by mutations in numerous human developmental disorders, ranging from diseases exclusively affecting brain development, through global growth failure syndromes to diverse pathologies associated with ciliary malfunction. Despite our much-improved understanding of centrosome function in cellular processes, we know remarkably little of its role in the organismal context, especially in mammals. In this review, we examine how centrosome dysfunction impacts on complex physiological processes and speculate on the challenges we face when applying knowledge generated from in vitro and in vivo model systems to human development.

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“…We now know that these pathways normally act in concert to enhance the timeliness and fidelity of spindle assembly in animal cells. Indeed, when centrioles are not present in animal somatic cells, the fidelity of bipolar spindle assembly and fidelity of chromosome distribution in anaphase are significantly compromised [49,50].…”

Section: Centrioles Versus Centrosomesmentioning

confidence: 99%

One to only two: a short history of the centrosome and its duplication

Sluder

2014

Phil. Trans. R. Soc. B

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This review discusses some of the history of the fundamental, but not fully solved problem of how the centrosome duplicates from one to only two as the cell prepares for mitosis. We start with some of the early descriptions of the centrosome and the remarkably prescient but then controversial inferences drawn concerning its function in the cell. For more than 100 years, one of the most difficult issues for the concept of the centrosome has been to integrate observations that centrosomes appear to be important for spindle assembly in animal cells yet are not evident in higher plant cells and some animal cells. This stirred debate over the existence of centrosomes and their importance. A parallel debate concerned the role of the centrioles in organizing centrosomes. The relatively recent elucidation of bipolar spindle assembly around chromatin allows a re-examination of the role of centrioles in controlling centrosome duplication in animal cells. The problem of how centrosomes precisely double in preparation for mitosis in animal cells has now moved to the mystery of how only one procentriole is assembled at each mother centriole

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Loss of centrioles causes chromosomal instability in vertebrate somatic cells

Abstract: Centrosomes establish a mitotic spindle geometry that facilitates correct kinetochore–microtubule attachments, contributing to the fidelity of chromosome segregation.

Cited by 118 publications

References 53 publications

Acentriolar mitosis activates a p53-dependent apoptosis pathway in the mouse embryo

Acentriolar mitosis activates a p53-dependent apoptosis pathway in the mouse embryo

Small organelle, big responsibility: the role of centrosomes in development and disease

One to only two: a short history of the centrosome and its duplication

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