The universal eukaryotic DNA replication kinetics is the consequence of simple physicochemical rules resulting from the localisation of potential replication origins at discrete sites and the diffusion of limiting origin firing factors in the nuclear space.
Establishment of replication-timing involves Fkh1-dependent recruitment and execution of DDK function in G1 phase resulting in dynamic relocalization of origins within the nucleus in anticipation of CDK-dependent origin activation.
To regulate DNA copy number during development in Drosophila, the SUUR protein recruits Rif1 to replisomes where Rif1 inhibits replication fork progression, thus controlling copy number independently of origin firing.
Mapping DNA replication timing, allied to genetic analysis of a RecQ repair helicase, reveals that antigenic variation in the African trypanosome may be initiated by locus-specific, replication-derived sequence instability.
The pervasive transcription environment alters the efficiency of firing of replication origins, which are 'protected' by roadblock termination due to origin recognition complex (ORC) and pre-RC complexes.