Topoisomerase IIα is required for embryonic development and liver regeneration in zebrafish

Michael Dovey, E. Elizabeth Patton, Teresa Bowman, Trista North, Wolfram Goessling, Yi Zhou, Leonard I. Zon

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Topoisomerases solve the topological problems encountered by DNA throughout the lifetime of a cell. Topoisomerase IIα, 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 IIα (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 (US)
Pages (from-to)3746-3753
Number of pages8
JournalMolecular and cellular biology
Volume29
Issue number13
DOIs
StatePublished - Jul 1 2009

    Fingerprint

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this