Abstract
The reasons why some DNA replication origins fire earlier than others have remained elusive. New work by Gindin etal suggests that the distribution of replication origins, not their timing per se, is the major determinant of the timing of genome replication in human cells.
Highlights
The reasons why some DNA replication origins fire earlier than others have remained elusive
I n any eukaryotic genome, some regions replicate early, while others replicate late (Rhind & Gilbert, 2013). This observation applies at the level of individual origins and in metazoans—where the lower spatial resolution of replication timing profiles does not allow the identification of individual origins—it applies to replication domains, large regions (100 kb to 1 Mb) containing many origins
The first input is the “initiation probability landscape” (IPLS), the probability that replication will initiate at any particular site in the genome
Summary
The reasons why some DNA replication origins fire earlier than others have remained elusive. This result is reminiscent of the observation that replication timing is highly correlated with the 3D structure of the genome (Ryba et al, 2010) Both of these features—DNase accessibility and 3D conformation—integrate aspects of DNA sequence and chromatin modification and presumably report on the elements of genome structure with the largest influence on origin activity better than any other single genome feature. In any case, this remarkably simple result suggests that the distribution of DNase I hypersensitive sites accurately predicts the distribution of replication origins in the human genome
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