What influences DNA replication rate in budding yeast?
BACKGROUND
DNA replication begins at specific locations called replication origins, where helicase and polymerase act in concert to unwind and process the single DNA filaments. The sites of active DNA synthesis are called replication forks. The density of initiation events is low when replication forks travel fast, and is high when forks travel slowly. Despite the potential involvement of epigenetic factors, transcriptional regulation and nucleotide availability, the causes of differences in replication times during DNA synthesis have not been established satisfactorily, yet.


RESULTS
Here, we aimed at quantifying to which extent sequence properties contribute to the DNA replication time in budding yeast. We interpreted the movement of the replication machinery along the DNA template as a directed random walk, decomposing influences on DNA replication time into sequence-specific and sequence-independent components. We found that for a large part of the genome the elongation time can be well described by a global average replication rate, thus by a single parameter. However, we also showed that there are regions within the genomic landscape of budding yeast with highly specific replication rates, which cannot be explained by global properties of the replication machinery.


CONCLUSIONS
Computational models of DNA replication in budding yeast that can predict replication dynamics have rarely been developed yet. We show here that even beyond the level of initiation there are effects governing the replication time that can not be explained by the movement of the polymerase along the DNA template alone. This allows us to characterize genomic regions with significantly altered elongation characteristics, independent of initiation times or sequence composition.
Spiesser
Thomas W
TW
Theoretical Biophysics, Institute for Biology, Humboldt University Berlin, Berlin, Germany.
Diener
Christian
C
Barberis
Matteo
M
Klipp
Edda
E
D004261:DNA Replication; D004271:DNA, Fungal / Q000235:genetics*; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D007700:Kinetics; D008962:Models, Theoretical; D009068:Movement; D018741:Replication Origin; D004718:Saccharomycetales / Q000235:genetics*
D004271:DNA, Fungal; D004259:DNA-Directed DNA Polymerase