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Resolution of anaphase bridges in cancer cells

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Abstract

Chromosomal instability is a key step in the generation of the cancer cell karyotype. An indicator of unstable chromosomes is the presence of chromatin bridges during anaphase. We examined in detail the fate of anaphase bridges in cultured oral squamous cell carcinoma cells in real-time. Surprisingly, chromosomes in bridges typically resolve by breaking into multiple fragments. Often these fragments give rise to micronuclei (MN) at the end of mitosis. The formation of MN is shown to have important consequences for the cell. We found that MN have incomplete nuclear pore complex (NPC) formation and nuclear import defects and the chromatin within has greatly reduced transcriptional activity. Thus, a major consequence of the presence of anaphase bridges is the regular sequestration of chromatin into genetically inert MN. This represents another source of ongoing genetic instability in cancer cells.

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Abbreviations

GFP:

Green fluorescent protein

MN:

Micronucleus/micronuclei

DAPI:

4′, 6-Diamidino-2-phenylindole

NPC:

Nuclear pore complex

GR:

Glucocorticoid receptor

UTP:

Uridine 5′triphosphate

PolII:

RNA polymerase II

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Acknowledgements

The authors gratefully acknowledge: Dr. D. DeFranco for the gift of the GFP-GR, Dr. U. Surti for the JAR cells, Dr. C. Walsh for the anti-tubulin antibodies, Dr. C. Feghali for the anti-centromere antibodies, and the tissue bank of the Oral Cancer Center of Discovery of the University of Pittsburgh Medical Center and Dr. Jennifer Hunt for the tumor samples and the University of Pittsburgh Cancer Institute for material support. We also thank Dr. Nicholas Quintyne and Janet Reing for critical review of the manuscript. The work was supported by National Institutes of Health Grant P60DE13059 to Dr. Eugene N. Myers.

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Correspondence to William S. Saunders.

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Hoffelder, D.R., Luo, L., Burke, N.A. et al. Resolution of anaphase bridges in cancer cells. Chromosoma 112, 389–397 (2004). https://doi.org/10.1007/s00412-004-0284-6

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