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ZFIN ID: ZDB-PUB-060921-7
DNA Repair Protein Involved in Heart and Blood Development
Wang, Y., Shupenko, C.C., Melo, L.F., and Strauss, P.R.
Date: 2006
Source: Molecular and cellular biology 26(23): 9083-9093 (Journal)
Registered Authors: Strauss, Phyllis, Wang, Yi
Keywords: none
MeSH Terms:
  • Amino Acid Sequence
  • Animals
  • Conserved Sequence
  • DNA Repair*
  • DNA-(Apurinic or Apyrimidinic Site) Lyase/chemistry
  • DNA-(Apurinic or Apyrimidinic Site) Lyase/genetics
  • DNA-(Apurinic or Apyrimidinic Site) Lyase/isolation & purification
  • DNA-(Apurinic or Apyrimidinic Site) Lyase/metabolism*
  • Embryo, Nonmammalian
  • Gene Dosage
  • Heart/anatomy & histology
  • Heart/embryology*
  • Hematopoiesis/genetics
  • Hematopoiesis/physiology*
  • Histocytochemistry
  • Humans
  • In Situ Hybridization
  • Kinetics
  • Microinjections
  • Molecular Sequence Data
  • Mutation
  • Oligonucleotides, Antisense/pharmacology
  • RNA, Messenger/genetics
  • RNA, Messenger/metabolism
  • Recombinant Proteins/chemistry
  • Recombinant Proteins/metabolism
  • Sequence Homology, Amino Acid
  • Transcription Initiation Site
  • Zebrafish/embryology*
PubMed: 16966376 Full text @ Mol. Cell. Biol.
FIGURES
ABSTRACT
AP endonuclease 1, a key enzyme in repairing abasic sites in DNA, is an embryonic lethal in mice. We are examining its role in embryogenesis in zebrafish. Zebrafish contain two genomic copies (zfAPEX1a and b) with identical coding sequences. zfAPEX1b lacks introns. Recombinant protein (ZAP1) is highly homologous with and has the same enzymatic properties as its human orthologue. ZAP1 is highly expressed throughout development. Embryos microinjected with morpholino oligonucleotide (MO) targeting the translation start site (TS) die at approximately the midblastula transition (MBT) without apoptosis. They are rescued with mRNA for human WT APEX1 but not APEX1 encoding endonuclease defective protein. Rescued embryos develop dysmorphic hearts, pericardial edema, few erythrocytes, small eyes and abnormal notochords. Although the hearts in rescued embryos form defective loops ranging from no loop to one that is abnormally shaped, cardiac myosin (cmlc2) is present and contraction occurs. Embryos microinjected with MO targeting zfAPEX1a intron/exon junctions also pass the MBT with similar abnormalities. We conclude that AP endonuclease 1 is involved in both repairing DNA and regulating specific early stages of embryonic development.
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