title: CAF-1 is essential for Drosophila development and involved in the maintenance of epigenetic memory.
abstract: 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.
authors.affiliation: National Laboratory of Biomacromolecules and State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, The Chinese Academy of Sciences, Datun Road 15, Chaoyang District, Beijing 100101, China.
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Song
authors.forename: Feng
authors.initials: F
authors.lastname: He
authors.forename: Gengqiang
authors.initials: G
authors.lastname: Xie
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Guo
authors.forename: Yanjuan
authors.initials: Y
authors.lastname: Xu
authors.forename: Yixu
authors.initials: Y
authors.lastname: Chen
authors.forename: Xuehong
authors.initials: X
authors.lastname: Liang
authors.forename: Igor
authors.initials: I
authors.lastname: Stagljar
authors.forename: Dieter
authors.initials: D
authors.lastname: Egli
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
authors.forename: Renjie
authors.initials: R
authors.lastname: Jiao
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000196:embryology* / Q000378:metabolism; D044127:Epigenesis, Genetic; D005123:Eye / Q000196:embryology; D005260:Female; D020868:Gene Silencing; D008297:Male; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D016296:Mutagenesis; D056505:Retinoblastoma-Binding Protein 4; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: C489780:CNOT8 protein, human; C110251:Caf1-55 protein, Drosophila; D002868:Chromosomal Proteins, Non-Histone; D029721:Drosophila Proteins; D018832:Molecular Chaperones; D056505:Retinoblastoma-Binding Protein 4; D014157:Transcription Factors