Genome-wide DNA replication profile for Drosophila melanogaster: a link between transcription and replication timing

• Published in: Nature genetics Vol. 32; no. 3; pp. 438 - 442
• Main Authors: Schübeler, Dirk, Scalzo, David, Kooperberg, Charles, van Steensel, Bas, Delrow, Jeffrey, Groudine, Mark
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.11.2002; Nature Publishing Group
• Subjects: Agriculture; Animal Genetics and Genomics; Animals; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Bromodeoxyuridine - pharmacology; Cancer Research; Cell Cycle; Cell division; Cell Separation; Deoxyribonucleic acid; DNA; DNA Replication; DNA, Complementary - metabolism; Drosophila; Drosophila melanogaster - genetics; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Function; Genetic aspects; Genetic transcription; Genome; Genomes; Human Genetics; Hybridization; Insects; letter; Medical research; Molecular and cellular biology; Molecular genetics; Mutagenesis. Repair; Nucleic Acid Hybridization; Oligonucleotide Array Sequence Analysis; Physiological aspects; Polymerase Chain Reaction; Precipitin Tests; S Phase; Surveying; Time Factors; Transcription, Genetic; Yeast; United States; United States > US; Genetic mapping; Transcription; Arthropoda; Insecta; DNA; Replication; Timing; Invertebrata; Genome; Drosophila melanogaster; Diptera; Drosophilidae
• ISSN: 1061-4036; 1546-1718
• DOI: 10.1038/ng1005

Replication of the genome before mitotic cell division is a highly regulated process that ensures the fidelity of DNA duplication. DNA replication initiates at specific locations, termed origins of replication, and progresses in a defined temporal order during the S phase of the cell cycle. The relationship between replication timing and gene expression has been the subject of some speculation 1 . A recent genome-wide analysis in Saccharomyces cerevisiae showed no association between replication timing and gene expression 2 . In higher eukaryotes, the limited number of genomic loci analyzed has not permitted a firm conclusion regarding this association. To explore the relationship between DNA replication and gene expression in higher eukaryotes, we developed a strategy to measure the timing of DNA replication for thousands of genes in a single DNA array hybridization experiment. Using this approach, we generated a genome-wide map of replication timing for Drosophila melanogaster . Moreover, by surveying over 40% of all D. melanogaster genes, we found a strong correlation between DNA replication early in S phase and transcriptional activity. As this correlation does not exist in S. cerevisiae , this interplay between DNA replication and transcription may be a unique characteristic of higher eukaryotes.