CAF-1 is essential for Drosophila development and involved in the maintenance of epigenetic memory

Dev Biol. 2007 Nov 1;311(1):213-22. doi: 10.1016/j.ydbio.2007.08.039. Epub 2007 Aug 29.


DNA synthesis during S-phase and upon DNA repair is accompanied by chromatin assembly. The chromatin assembly factor CAF-1 has been biochemically well-characterized to deposit histones onto newly synthesized DNA. To gain insights into the in vivo functions of CAF-1 in Drosophila, we generated null mutants of the largest subunit of dCAF-1, dCAF-1-p180. We show that, unlike CAF-1 mutant yeast, dCAF-1-p180 mutant flies are hemizygous lethal. Removal of maternal dCAF-1-p180 activity by germline clones blocks oogenesis. Tissue-specific deletion of dCAF-1-p180 in the eye primordia disrupts eye development. In addition, reduction of dCAF-1-p180 activity suppresses gene silencing at heterochromatin and antagonizes Polycomb-mediated cell fate determination. Furthermore, heterozygous dCAF-1-p180 mutant flies display an increased sensitivity to gamma-irradiation and a reduced efficiency in recombinational double strand break (DSB) repair. Our experiments also show that human hCAF-1-p150 can rescue the dCAF-1-p180 mutant flies, demonstrating a functional conservation of eukaryotic CAF-1 activities in vivo. Together, our results establish that dCAF-1-p180 is an essential gene for Drosophila development and further underscore the importance of dCAF-1 in regulating gene expression and DNA repair in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / embryology*
  • Drosophila melanogaster / metabolism
  • Epigenesis, Genetic*
  • Eye / embryology
  • Female
  • Gene Silencing
  • Male
  • Molecular Chaperones / genetics
  • Molecular Chaperones / metabolism*
  • Mutagenesis
  • Retinoblastoma-Binding Protein 4
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*


  • CNOT8 protein, human
  • Caf1-55 protein, Drosophila
  • Chromosomal Proteins, Non-Histone
  • Drosophila Proteins
  • Molecular Chaperones
  • Retinoblastoma-Binding Protein 4
  • Transcription Factors