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Growth disadvantage associated with centrosome amplification drives population-level centriole number homeostasis

The centriole duplication cycle normally ensures that centriole number is maintained at two centrioles per G1 cell. However, some circumstances can result in an aberrant increase in centriole number—a phenotype that is particularly prevalent in several types of cancer. Following an artificial increa...

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Detalles Bibliográficos
Autores principales: Sala, Roberta, Farrell, KC, Stearns, Tim
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927180/
https://www.ncbi.nlm.nih.gov/pubmed/32966175
http://dx.doi.org/10.1091/mbc.E19-04-0195
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author Sala, Roberta
Farrell, KC
Stearns, Tim
author_facet Sala, Roberta
Farrell, KC
Stearns, Tim
author_sort Sala, Roberta
collection PubMed
description The centriole duplication cycle normally ensures that centriole number is maintained at two centrioles per G1 cell. However, some circumstances can result in an aberrant increase in centriole number—a phenotype that is particularly prevalent in several types of cancer. Following an artificial increase in centriole number without tetraploidization due to transient overexpression of the kinase PLK4, human cells return to a normal centriole number during the proliferation of the population. We examine the mechanisms responsible for this return to normal centriole number at the population level in human retinal pigment epithelial cells. We find that the return to normal centriole number in the population of induced cells cannot be explained by limited duplication of centrioles, instability of extra centrioles, or by grossly asymmetric segregation of extra centrioles in mitosis. However, cells with extra centrioles display heterogenous phenotypes including extended cell cycle arrest, longer interphase durations, and death, which overall results in a proliferative disadvantage relative to normal cells in the population. Although about half of cells with extra centrioles in a population were able to divide, the extent of the disadvantages conferred by other fates is sufficient to account for the observed rate of return to normal centriole number. These results suggest that only under conditions of positive selection for cells with extra centrioles, continuous generation of such centrioles, or alleviation of the disadvantageous growth phenotypes would they be maintained in a population.
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spelling pubmed-79271802021-03-03 Growth disadvantage associated with centrosome amplification drives population-level centriole number homeostasis Sala, Roberta Farrell, KC Stearns, Tim Mol Biol Cell Brief Reports The centriole duplication cycle normally ensures that centriole number is maintained at two centrioles per G1 cell. However, some circumstances can result in an aberrant increase in centriole number—a phenotype that is particularly prevalent in several types of cancer. Following an artificial increase in centriole number without tetraploidization due to transient overexpression of the kinase PLK4, human cells return to a normal centriole number during the proliferation of the population. We examine the mechanisms responsible for this return to normal centriole number at the population level in human retinal pigment epithelial cells. We find that the return to normal centriole number in the population of induced cells cannot be explained by limited duplication of centrioles, instability of extra centrioles, or by grossly asymmetric segregation of extra centrioles in mitosis. However, cells with extra centrioles display heterogenous phenotypes including extended cell cycle arrest, longer interphase durations, and death, which overall results in a proliferative disadvantage relative to normal cells in the population. Although about half of cells with extra centrioles in a population were able to divide, the extent of the disadvantages conferred by other fates is sufficient to account for the observed rate of return to normal centriole number. These results suggest that only under conditions of positive selection for cells with extra centrioles, continuous generation of such centrioles, or alleviation of the disadvantageous growth phenotypes would they be maintained in a population. The American Society for Cell Biology 2020-11-15 /pmc/articles/PMC7927180/ /pubmed/32966175 http://dx.doi.org/10.1091/mbc.E19-04-0195 Text en © 2020 Sala et al. “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. http://creativecommons.org/licenses/by-nc-sa/3.0 This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License.
spellingShingle Brief Reports
Sala, Roberta
Farrell, KC
Stearns, Tim
Growth disadvantage associated with centrosome amplification drives population-level centriole number homeostasis
title Growth disadvantage associated with centrosome amplification drives population-level centriole number homeostasis
title_full Growth disadvantage associated with centrosome amplification drives population-level centriole number homeostasis
title_fullStr Growth disadvantage associated with centrosome amplification drives population-level centriole number homeostasis
title_full_unstemmed Growth disadvantage associated with centrosome amplification drives population-level centriole number homeostasis
title_short Growth disadvantage associated with centrosome amplification drives population-level centriole number homeostasis
title_sort growth disadvantage associated with centrosome amplification drives population-level centriole number homeostasis
topic Brief Reports
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927180/
https://www.ncbi.nlm.nih.gov/pubmed/32966175
http://dx.doi.org/10.1091/mbc.E19-04-0195
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