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

Nat Genet. 2002 Nov;32(3):438-42. doi: 10.1038/ng1005. Epub 2002 Sep 30.


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. A recent genome-wide analysis in Saccharomyces cerevisiae showed no association between replication timing and gene expression. 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bromodeoxyuridine / pharmacology
  • Cell Cycle
  • Cell Separation
  • DNA Replication*
  • DNA, Complementary / metabolism
  • Drosophila melanogaster / genetics*
  • Flow Cytometry
  • Genome
  • Nucleic Acid Hybridization
  • Oligonucleotide Array Sequence Analysis
  • Polymerase Chain Reaction
  • Precipitin Tests
  • S Phase
  • Time Factors
  • Transcription, Genetic*


  • DNA, Complementary
  • Bromodeoxyuridine