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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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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2020
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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. |
format | Online Article Text |
id | pubmed-7927180 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
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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