Evaluating genome-scale approaches to eukaryotic DNA replication

Mechanisms regulating where and when eukaryotic DNA replication initiates remain a fundamental mystery in molecular biology.Genome-scale approaches are now being used to identify the location of replication origins and to evaluate replication timing.Mapping replication origins in yeasts has been successful, but the current data sets from multicellular organisms are scarce and inconsistent.Methods for mapping origins include trapping the earliest replicated DNA by replication fork arrest, mapping small nascent leading strands and trapping replication bubbles.Studies of replication timing can involve prospective or retroactive synchronization of cells, followed by comparison of early- and late-S-phase DNA by microarray or sequencing.Genome-wide studies of replication timing have shown that timing is regulated at the level of replication domains and that there are links between replication timing and chromatin structure.