E2F mediates developmental and cell cycle regulation of ORC1 in Drosophila.
Throughout the cell cycle of Saccharomyces cerevisiae, the level of origin recognition complex (ORC) is constant and ORCs are bound constitutively to replication origins. Replication is regulated by the recruitment of additional factors such as CDC6. ORC components are widely conserved, and it generally has been assumed that they are also stable factors bound to origins throughout the cell cycle. In this report, we show that the level of the ORC1 subunit changes dramatically throughout Drosophila development. The accumulation of ORC1 is regulated by E2F-dependent transcription. In embryos, ORC1 accumulates preferentially in proliferating cells. In the eye imaginal disc, ORC1 accumulation is cell cycle regulated, with high levels in late G1 and S phase. In the ovary, the sub-nuclear distribution of ORC1 shifts during a developmentally regulated switch from endoreplication of the entire genome to amplification of the chorion gene clusters. Furthermore, we find that overexpression of ORC1 alters the pattern of DNA synthesis in the eye disc and the ovary. Thus, replication origin activity appears to be governed in part by the level of ORC1 in Drosophila.
Asano
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Howard Hughes Medical Institute, Department of Genetics, Box 3657, Duke University Medical Center, Durham, NC 27710, USA.
Wharton
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RP
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002352:Carrier Proteins; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D004330:Drosophila / Q000166:cytology* / Q000196:embryology; D029721:Drosophila Proteins; D050684:E2F Transcription Factors; D005123:Eye / Q000196:embryology; D008969:Molecular Sequence Data; D009024:Morphogenesis; D051738:Origin Recognition Complex; D011401:Promoter Regions, Genetic; D056465:Retinoblastoma-Binding Protein 1; D014018:Tissue Distribution; D015534:Trans-Activators; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C088053:Dp transcription factor, Drosophila; D029721:Drosophila Proteins; D050684:E2F Transcription Factors; C497213:Orc1 protein, Drosophila; D051738:Origin Recognition Complex; D056465:Retinoblastoma-Binding Protein 1; D015534:Trans-Activators; D014157:Transcription Factors