title: Maternal topoisomerase II alpha, not topoisomerase II beta, enables embryonic development of zebrafish top2a-/- mutants.
abstract: BACKGROUND
  Genetic alterations in human topoisomerase II alpha (TOP2A) are linked to cancer susceptibility. TOP2A decatenates chromosomes and thus is necessary for multiple aspects of cell division including DNA replication, chromosome condensation and segregation. Topoisomerase II alpha is also required for embryonic development in mammals, as mouse Top2a knockouts result in embryonic lethality as early as the 4-8 cell stage. The purpose of this study was to determine whether the extended developmental capability of zebrafish top2a mutants arises from maternal expression of top2a or compensation from its top2b paralogue.
  
  
  RESULTS
  Here, we describe bloody minded (blm), a novel mutant of zebrafish top2a. In contrast to mouse Top2a nulls, zebrafish top2a mutants survive to larval stages (4-5 day post fertilization). Developmental analyses demonstrate abundant expression of maternal top2a but not top2b. Inhibition or poisoning of maternal topoisomerase II delays embryonic development by extending the cell cycle M-phase. Zygotic top2a and top2b are co-expressed in the zebrafish CNS, but endogenous or ectopic top2b RNA appear unable to prevent the blm phenotype.
  
  
  CONCLUSIONS
  We conclude that maternal top2a enables zebrafish development before the mid-zygotic transition (MZT) and that zebrafish top2a and top2b are not functionally redundant during development after activation of the zygotic genome.
authors: UCD School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Dublin, Ireland.
authors: Beata
authors: B
authors: Sapetto-Rebow
authors: Sarah C
authors: SC
authors: McLoughlin
authors: Lynne C
authors: LC
authors: O'Shea
authors: Olivia
authors: O
authors: O'Leary
authors: Jason R
authors: JR
authors: Willer
authors: Yolanda
authors: Y
authors: Alvarez
authors: Ross
authors: R
authors: Collery
authors: Jacintha
authors: J
authors: O'Sullivan
authors: Freek
authors: F
authors: Van Eeden
authors: Carmel
authors: C
authors: Hensey
authors: Breandán N
authors: BN
authors: Kennedy
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D001483:Base Sequence; D002453:Cell Cycle; D002457:Cell Extracts; D004250:DNA Topoisomerases, Type II / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D054659:Diketopiperazines; D047108:Embryonic Development; D005260:Female; D015870:Gene Expression; D055786:Gene Knockout Techniques; D005808:Genes, Recessive; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D008297:Male; D010641:Phenotype; D010802:Phylogeny; D010879:Piperazines / Q000494:pharmacology; D017354:Point Mutation; D000075223:Poly-ADP-Ribose Binding Proteins; D017422:Sequence Analysis, DNA; D052286:Viviparity, Nonmammalian; D014981:Xenopus; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015053:Zygote / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D002457:Cell Extracts; D004268:DNA-Binding Proteins; D054659:Diketopiperazines; D007527:Isoenzymes; D010879:Piperazines; D000075223:Poly-ADP-Ribose Binding Proteins; D029961:Zebrafish Proteins; C070899:4,4'-(1,2-dimethyl-1,2-ethanediyl)bis-2,6-piperazinedione; D004250:DNA Topoisomerases, Type II; C000618811:TOP2A protein, human; C000618814:TOP2B protein, human; C000618812:Top2a protein, mouse; C000618815:Top2b protein, mouse