Genome-wide model for the normal eukaryotic DNA replication fork

摘要

To investigate DNA replication enzymology across the nuclear genome rnof budding yeast deep sequencing was used to establish the pattern of unconnected replication errors generated by an asymmetric rnmutator variant of DNA polymerase δ (Pol δ). Sequencing of 16 genomes identified 1,206-bp substitutions generated over 33 generations rnby L612M Pol δ in a mismatch repair defective strain. Alignment rnof sequences flanking these substitutions identified "hotspof' motifs for Pol 6 replication errors. The substitutions were distributed evenly across all 16 chromosomes. The vast majority were transitions that occurred with a strand bias that varied in a predictable manner relative to known functional origins of replication. This strand bias strongly supports the idea that Pol δ is primarily a lagging strand polymerase during replication across the entire nuclear genome.