Topoisomerase II Is Required for Embryonic Development and Liver Regeneration in Zebrafish

M. Dovey, E Elizabeth Patton, T. Bowman, T. North, W. Goessling, Y. Zhou, L. I. Zon

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Topoisomerases solve the topological problems encountered by DNA throughout the lifetime of a cell. Topoisomerase II, which is highly conserved among eukaryotes, untangles replicated chromosomes during mitosis and is absolutely required for cell viability. A homozygous lethal mutant, can4, was identified in a screen to identify genes important for cell proliferation in zebrafish by utilizing an antibody against a mitosis-specific marker, phospho-histone H3. Mutant embryos have a decrease in the number of proliferating cells and display increases in DNA content and apoptosis, as well as mitotic spindle defects. Positional cloning revealed that the genetic defect underlying these phenotypes was the result of a mutation in the zebrafish topoisomerase II(top2a) gene. top2a was found to be required for decatenation but not for condensation in embryonic mitoses. In addition to being required for development, top2a was found to be a haploinsufficient regulator of adult liver regrowth in zebrafish. Regeneration analysis of other adult tissues, including fins, revealed no heterozygous phenotype. Our results confirm a conserved role for TOP2A in vertebrates as well as a dose-sensitive requirement for top2a in adults.
Original languageEnglish
Pages (from-to)3746-3753
Number of pages8
JournalMolecular and Cellular Biology
Issue number13
Publication statusPublished - Jul 2009

Keywords / Materials (for Non-textual outputs)

  • animals
  • Antigens, Neoplasm
  • Base Sequence
  • Chromosomes
  • DNA Topoisomerases, Type II
  • DNA-Binding Proteins
  • Female
  • Isoenzymes
  • Liver Regeneration
  • Male
  • Molecular Sequence Data
  • Zebrafish Proteins


Dive into the research topics of 'Topoisomerase II Is Required for Embryonic Development and Liver Regeneration in Zebrafish'. Together they form a unique fingerprint.

Cite this