Figure 1. Organization of replication origins, replicons and replication-timing domains.

a | An illustration of a portion of a eukaryotic chromosome depicting five replicons, each defined by an origin of replication (A, B, C, D and E). Replication starts at different times during the S phase of the cell cycle. Origins A, B and C start replication first, concomitantly or in immediate succession, followed later by the initiation of DNA replication from origins D and E. The replicons containing origins A, B and C form an early replication-timing domain, and the replicons containing origins D and E form a late replication-timing domain. b | An example of possible replication-timing measurements revealing large megabase-sized replication-timing domains. Chromatin domains with similar replication timing (top panel) exhibit a similar copy number in an asynchronous cell population, with early-replicating domains (such as the domain including replicons A, B and C) containing more copies than late-replicating domains (such as the domain including replicons D and E). High-resolution mapping of replication timing (bottom panel) reveals subpeaks (indicated by white arrows) in large replication domains that correspond to individual replicons driven by distinct replication origins (for example, the subpeaks for origins A, B and C are visible within the large early-replicating domain). c | Nuclear distribution of replicons and replication domains. Replicating DNA (represented by ellipses) tends to cluster, with each replication cluster containing adjacent, concomitantly replicating regions with several active origins. Early-replicating clusters usually associate with open chromatin (euchromatin; typically in the centre of the nucleus). Late-replicating clusters (here shown containing origins that have not yet started replication, depicted as dark red circles) associate with silent, transcriptionally inactive chromatin (facultative and constitutive heterochromatin; typically near the nuclear envelope). Highly transcribed chromatin often replicates early during S phase, but replication rarely initiates within actively transcribed regions.