Journal article
Interphase cytofission maintains genomic integrity of human cells after failed cytokinesis
Proceedings of the National Academy of Sciences - PNAS, Vol.110(32), pp.13026-13031
08/06/2013
DOI: 10.1073/pnas.1308203110
PMCID: PMC3740861
PMID: 23878225
Abstract
In cell division, cytokinesis is tightly coupled with mitosis to maintain genomic integrity. Failed cytokinesis in humans can result in tetraploid cells that can become aneuploid and promote cancer. However, the likelihood of aneuploidy and cancer after a failed cytokinesis event is unknown. Here we evaluated cell fate after failed cytokinesis. We interrupted cytokinesis by brief chemical treatments in cell populations of human epithelial lines. Surprisingly, up to 50% of the resulting binucleate cells generated colonies. In RPE1 cells, 90% of colonies obtained from binucleate founders had a karyotype that matched the parental cell type. Time-lapse videomicroscopy demonstrated that binucleate cells are delayed in the first growth phase of the cell cycle (G1) and undergo interphase cellular fission (cytofission) that distributes nuclei into separate daughters. The fission is not compatible with delayed cytokinesis because events occur in the absence of polymerized microtubules and without canonical components of the cytokinetic machinery. However, the cytofission can be interrupted by inhibiting function of actin or myosin II. Fission events occur in both two- and three-dimensional culture. Our data demonstrate that cytofission can preserve genomic integrity after failed cytokinesis. Thus, traction-mediated cytofission, originally observed in Dictyostelium, is relevant to human biology-where it seems to be an evolutionarily conserved mechanism that can preserve genomic integrity.
Details
- Title: Subtitle
- Interphase cytofission maintains genomic integrity of human cells after failed cytokinesis
- Creators
- Alka Choudhary - Univ Wisconsin, Carbone Canc Ctr, Madison, WI 53705 USARobert F. Lera - Univ Wisconsin, Carbone Canc Ctr, Madison, WI 53705 USAMelissa L. Martowicz - Univ Wisconsin, Carbone Canc Ctr, Madison, WI 53705 USAKim Oxendine - Univ Wisconsin, Wisconsin State Lab Hyg, Madison, WI 53706 USAJennifer J. Laffin - Univ Wisconsin, Wisconsin State Lab Hyg, Madison, WI 53706 USABeth A. Weaver - Univ Wisconsin, Carbone Canc Ctr, Madison, WI 53705 USAMark E. Burkard - Univ Wisconsin, Carbone Canc Ctr, Madison, WI 53705 USA
- Resource Type
- Journal article
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.110(32), pp.13026-13031
- DOI
- 10.1073/pnas.1308203110
- PMID
- 23878225
- PMCID
- PMC3740861
- NLM abbreviation
- Proc Natl Acad Sci U S A
- ISSN
- 0027-8424
- eISSN
- 1091-6490
- Publisher
- Natl Acad Sciences
- Number of pages
- 6
- Grant note
- Flight Attendant Medical Research Institute P30CA014520 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) IRG-58-011-48 / American Cancer Society UL1TR000427 / NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Advancing Translational Sciences (NCATS) R01 GM097245 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA P30 CA14520 / University of Wisconsin Carbone Cancer Center UL1RR025011 / NATIONAL CENTER FOR RESEARCH RESOURCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Research Resources (NCRR) R01GM097245 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) 1UL1RR025011 / Mary Kay Ash Foundation Clinical, Translational Science Award
- Language
- English
- Date published
- 08/06/2013
- Academic Unit
- Internal Medicine
- Record Identifier
- 9984701253802771
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