Home LiteratureArticle Details
PMID: 15156327 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Resolution of anaphase bridges in cancer cells.

Chromosoma ·Vol. 112 ·No. 8 ·2004-06-00 ·Pages 389-97

Hoffelder DR, Luo L, Burke NA, Watkins SC, Gollin SM, Saunders WS

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.

MeSH Terms
Anaphase/genetics Carcinoma, Squamous Cell/genetics,pathology Cell Nucleus/metabolism Chromatin/genetics Chromosomal Instability Humans Micronuclei, Chromosome-Defective Mouth Neoplasms/genetics,pathology Transcription, Genetic Tumor Cells, Cultured
Chemicals
Chromatin
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Hoffelder Diane R
Department of Biological Sciences, University of Pittsburgh, 258 Crawford Hall, 15260, Pittsburgh, PA 15260, USA.
Luo Li
Burke Nancy A
Watkins Simon C
Gollin Susanne M
Saunders William S
References (53)
53 references, click to expand
  1. Chromosome segregation and cancer: cutting through the mystery.
    Nat Rev Cancer. 2001 Nov;1(2):109-17 PMID: 11905802
  2. Incorporation of macromolecules into living cells.
    Methods Cell Biol. 1989;29:153-73 PMID: 2643758
  3. Human lymphocytes micronucleus assay in Europe. An international survey.
    Mutat Res. 1997 Aug 1;392(1-2):165-74 PMID: 9269340
  4. Building and breaking bridges between sister chromatids.
    Bioessays. 2003 Dec;25(12):1178-91 PMID: 14635253
  5. Telomere dysfunction and evolution of intestinal carcinoma in mice and humans.
    Nat Genet. 2001 Jun;28(2):155-9 PMID: 11381263
  6. Cytokinesis-block micronucleus assay in WIL2-NS cells: a sensitive system to detect chromosomal damage induced by reactive oxygen species and activated human neutrophils.
    Mutagenesis. 2000 May;15(3):261-9 PMID: 10792021
  7. CINE-MICROGRAPHIC STUDIES ON DICENTRIC CHROMOSOMES.
    Chromosoma. 1964 Dec 10;15:630-51 PMID: 14333155
  8. Condensin-dependent localisation of topoisomerase II to an axial chromosomal structure is required for sister chromatid resolution during mitosis.
    J Cell Sci. 2003 Dec 1;116(Pt 23):4763-76 PMID: 14600262
  9. A nuclear pore complex protein that contains zinc finger motifs, binds DNA, and faces the nucleoplasm.
    Cell. 1993 Jan 15;72(1):29-38 PMID: 8422679
  10. Fifty years of amanitin.
    Experientia. 1991 Dec 1;47(11-12):1186-93 PMID: 1765129
  11. Inclusion of micronuclei in non-divided mononuclear lymphocytes and necrosis/apoptosis may provide a more comprehensive cytokinesis block micronucleus assay for biomonitoring purposes.
    Mutagenesis. 2001 Jan;16(1):51-8 PMID: 11139598
  12. Dislocation of chromatin elements in prophase induced by diethylstilbestrol: a novel mechanism by which micronuclei can arise.
    Mutat Res. 1991 Jan;246(1):113-22 PMID: 1898765
  13. Abnormal nuclear shape in solid tumors reflects mitotic instability.
    Am J Pathol. 2001 Jan;158(1):199-206 PMID: 11141493
  14. Hydroperoxide-induced DNA damage and mutations.
    Mutat Res. 2000 May 30;450(1-2):107-24 PMID: 10838137
  15. The making of the mitotic chromosome: modern insights into classical questions.
    Mol Cell. 2003 Mar;11(3):557-69 PMID: 12667441
  16. The genetic toxicity of human carcinogens and its implications.
    Mutat Res. 1988 Jan;204(1):3-15 PMID: 3277048
  17. Nucleoplasmic bridges are a sensitive measure of chromosome rearrangement in the cytokinesis-block micronucleus assay.
    Mutagenesis. 2003 Mar;18(2):187-94 PMID: 12621075
  18. Observations of radiation-induced chromosome fragment loss in live mammalian cells in culture, and its effect on colony-forming ability.
    Int J Radiat Biol Relat Stud Phys Chem Med. 1981 Apr;39(4):395-408 PMID: 6971848
  19. Telomere length dynamics and chromosomal instability in cells derived from telomerase null mice.
    J Cell Biol. 1999 Feb 22;144(4):589-601 PMID: 10037783
  20. Micronuclei in vivo.
    Prog Clin Biol Res. 1990;340B:185-94 PMID: 2203005
  21. Rationale for selecting exfoliated bladder cell micronuclei as potential biomarkers for arsenic genotoxicity.
    J Toxicol Environ Health. 1993 Oct-Nov;40(2-3):223-34 PMID: 8230298
  22. Hereditary and environmental factors associated with risk and progression of head and neck cancer.
    Otolaryngol Clin North Am. 1992 Oct;25(5):1089-103 PMID: 1408193
  23. Growth-related changes in phosphorylation of yeast RNA polymerase II.
    J Biol Chem. 1998 Feb 20;273(8):4689-94 PMID: 9468530
  24. Co-amplified markers alternate in megabase long chromosomal inverted repeats and cluster independently in interphase nuclei at early steps of mammalian gene amplification.
    EMBO J. 1992 Jul;11(7):2665-73 PMID: 1628626
  25. Micronuclei as an index of cytogenetic damage: past, present, and future.
    Environ Mol Mutagen. 1991;18(4):277-91 PMID: 1748091
  26. Identification and characterization of a nuclear pore complex protein.
    Cell. 1986 Jun 6;45(5):699-709 PMID: 3518946
  27. Important variables that influence base-line micronucleus frequency in cytokinesis-blocked lymphocytes-a biomarker for DNA damage in human populations.
    Mutat Res. 1998 Aug 3;404(1-2):155-65 PMID: 9729354
  28. DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139.
    J Biol Chem. 1998 Mar 6;273(10):5858-68 PMID: 9488723
  29. High-resolution mapping of the 11q13 amplicon and identification of a gene, TAOS1, that is amplified and overexpressed in oral cancer cells.
    Proc Natl Acad Sci U S A. 2002 Aug 20;99(17):11369-74 PMID: 12172009
  30. Analysis of anaphase figures in routine histologic sections distinguishes chromosomally unstable from chromosomally stable malignancies.
    Cancer Biol Ther. 2003 May-Jun;2(3):248-52 PMID: 12878857
  31. Telomere dysfunction promotes non-reciprocal translocations and epithelial cancers in mice.
    Nature. 2000 Aug 10;406(6796):641-5 PMID: 10949306
  32. Chromosome instability in cancer: how, when, and why?
    Adv Cancer Res. 2003;87:1-29 PMID: 12641272
  33. Cytostellin distributes to nuclear regions enriched with splicing factors.
    J Cell Sci. 1994 Mar;107 ( Pt 3):387-96 PMID: 8006060
  34. The relationship between spontaneous telomere loss and chromosome instability in a human tumor cell line.
    Neoplasia. 2000 Nov-Dec;2(6):540-54 PMID: 11228547
  35. The cytokinesis-block micronucleus technique: a detailed description of the method and its application to genotoxicity studies in human populations.
    Mutat Res. 1993 Jan;285(1):35-44 PMID: 7678131
  36. Chromosome pulverization in human cells with micronuclei.
    J Natl Cancer Inst. 1968 Jan;40(1):165-79 PMID: 5635016
  37. Chromosome aberrations, micronuclei, aneuploidy, sister chromatid exchanges, and cancer risk assessment.
    Mutat Res. 1996 Sep;365(1-3):147-59 PMID: 8898995
  38. The in vitro micronucleus test: a multi-endpoint assay to detect simultaneously mitotic delay, apoptosis, chromosome breakage, chromosome loss and non-disjunction.
    Mutat Res. 1997 Aug 1;392(1-2):19-30 PMID: 9269328
  39. The contribution of the mouse spermatid micronucleus assay to the detection of germinal mutagens.
    Prog Clin Biol Res. 1991;372:513-20 PMID: 1956944
  40. Evidence using a green fluorescent protein-glucocorticoid receptor chimera that the Ran/TC4 GTPase mediates an essential function independent of nuclear protein import.
    J Cell Biol. 1996 Jun;133(5):985-96 PMID: 8655589
  41. Protection of mammalian telomeres.
    Oncogene. 2002 Jan 21;21(4):532-40 PMID: 11850778
  42. What do human micronuclei contain?
    Mutagenesis. 2003 May;18(3):221-33 PMID: 12714687
  43. Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation.
    J Cell Biol. 1992 Nov;119(3):493-501 PMID: 1400587
  44. Methods used to study structure and function of the nucleolus.
    Methods Cell Biol. 1998;53:303-21 PMID: 9348514
  45. Considerations in the U.S. Environmental Protection Agency's testing approach for mutagenicity.
    Mutat Res. 1991 Nov;258(3):259-83 PMID: 1719404
  46. The persistence of micronucleated erythrocytes in the peripheral circulation of normal and splenectomized Fischer 344 rats: implications for cytogenetic screening.
    Mutat Res. 1984 Jul;127(2):169-74 PMID: 6749161
  47. Nuclear pore complexes form immobile networks and have a very low turnover in live mammalian cells.
    J Cell Biol. 2001 Jul 9;154(1):71-84 PMID: 11448991
  48. RNA polymerase activity in PtK1 micronuclei containing individual chromosomes. An in vitro and in situ study.
    Exp Cell Res. 1987 Mar;169(1):233-44 PMID: 3817015
  49. Application of the in vitro rat hepatocyte micronucleus assay in genetic toxicology testing.
    Mutat Res. 1997 Aug 1;392(1-2):125-38 PMID: 9269337
  50. Classification of micronuclei in murine erythrocytes: immunofluorescent staining using CREST antibodies compared to in situ hybridization with biotinylated gamma satellite DNA.
    Mutagenesis. 1991 Jul;6(4):297-302 PMID: 1719336
  51. [Micronucleus and cytogenetic disorders in mouse embryos before implantation].
    Tsitol Genet. 1977 Jan-Feb;11(1):17-22 PMID: 578340
  52. Histone-GFP fusion protein enables sensitive analysis of chromosome dynamics in living mammalian cells.
    Curr Biol. 1998 Mar 26;8(7):377-85 PMID: 9545195
  53. The present state of the automated micronucleus test for lymphocytes.
    Int J Radiat Biol. 1990 Nov;58(5):813-25 PMID: 1977825
Article Info
Journal
Chromosoma
Abbr.
Chromosoma
ISSN
0009-5915
DOI
10.1007/s00412-004-0284-6
Published
2004-06-00
Epub
2004-00-20
Pages
389-97
Language
English
Region
Austria
NLM ID
2985138R
Subset
IM
Grants
NIDCR NIH HHS · P60DE13059 · United States
External Links
PubMed source DOI: 10.1007/s00412-004-0284-6 View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2