The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.
Merotelic kinetochore orientation versus chromosome mono-orientation in the origin of lagging chromosomes in human primary cells
Abstract
Defects in chromosome segregation play a critical role in producing genomic instability and aneuploidy, which are associated with congenital diseases and carcinogenesis. We recently provided evidence from immunofluorescence and electron microscopy studies that merotelic kinetochore orientation is a major mechanism for lagging chromosomes during mitosis in PtK1 cells. Here we investigate whether human primary fibroblasts exhibit similar errors in chromosome segregation and if at least part of lagging chromosomes may arise in cells entering anaphase in the presence of mono-oriented chromosomes. By using in situ hybridization with alphoid probes to chromosome 7 and 11 we showed that loss of a single sister is much more frequent than loss of both sisters from the same chromosome in anatelophases from human primary fibroblasts released from a nocodazole-induced mitotic arrest, as predicted from merotelic orientation of single kinetochores. Furthermore, the lagging of pairs of separated sisters was higher than expected from random chance indicating that merotelic orientation of one sister may promote merotelic orientation of the other. Kinetochores of lagging chromosomes in anaphase human cells were found to be devoid of the mitotic checkpoint phosphoepitopes recognized by the 3F3/2 antibody, suggesting that they attached kinetochore microtubules prior to anaphase onset. Live cell imaging of H2B histone-GFP-transfected cells showed that cells with mono-oriented chromosomes never enter anaphase and that lagging chromosomes appear during anaphase after chromosome alignment occurs during metaphase. Thus, our results demonstrate that the mitotic checkpoint efficiently prevents the possible aneuploid burden due to mono-oriented chromosomes and that merotelic kinetochore orientation is a major limitation for accurate chromosome segregation and a potentially important mechanism of aneuploidy in human cells.
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Citations
Cites
Genetic instabilities in human cancers
Lengauer, C., Kinzler, K. W., & Vogelstein, B. (1998) · Nature · doi:10.1038/25292 · Cited by 4,168
Human Zw10 and ROD are mitotic checkpoint proteins that bind to kinetochores
Chan, G. K. T., Jablonski, S. A., Starr, D. A., Goldberg, M. L., & Yen, T. J. (2000) · Nature Cell Biology · doi:10.1038/35046598 · Cited by 217
Cited by
Boveri revisited: chromosomal instability, aneuploidy and tumorigenesis
Holland, A. J., & Cleveland, D. W. (2009) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2718 · Cited by 859
Lan, W., Zhang, X., Kline-Smith, S. L., Rosasco, S. E., Barrett-Wilt, G. A., Shabanowitz, J., Hunt, D. F., Walczak, C. E., & Stukenberg, P. T. (2004) · Current Biology · doi:10.1016/j.cub.2004.01.055 · Cited by 469
Aurora Kinase Promotes Turnover of Kinetochore Microtubules to Reduce Chromosome Segregation Errors
Cimini, D., Wan, X., Hirel, C. B., & Salmon, E. D. (2006) · Current Biology · doi:10.1016/j.cub.2006.07.022 · Cited by 401
Self-citationWhat do human micronuclei contain?
Norppa, H. (2003) · Mutagenesis · doi:10.1093/mutage/18.3.221 · Cited by 389
Holland, A. J., & Cleveland, D. W. (2012) · EMBO reports · doi:10.1038/embor.2012.55 · Cited by 288
Metadata
- Authors
- Cimini, D., Fioravanti, D., Salmon, E. D., & Degrassi, F.
- Venue
- Journal of Cell Science
- Publisher
- The Company of Biologists
- Published
- 2002-02-01
- Volume
- 115
- Issue
- 3
- Pages
- 507-515
- ISSN
- 0021-9533 (ISSN-L)
- 1477-9137
- OpenAlex
- W1522090640
- Cited by
- 161
- References
- 2
- FWCI
- 2.74
- Type
- journal article
- Language
- en
- Open access
- closed
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- Cimini, D., Fioravanti, D., Salmon, E. D., & Degrassi, F. (2002). Merotelic kinetochore orientation versus chromosome mono-orientation in the origin of lagging chromosomes in human primary cells. Journal of Cell Science. https://doi.org/10.1242/jcs.115.3.507
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