ReplikationsoriginEnsembles

Replikationsorigin, or origin of replication, is a DNA sequence where replication begins, marking the start of a replicon. In bacteria, replication initiates at a single oriC locus. The initiator protein DnaA binds to DnaA boxes, destabilizing an AT-rich region and facilitating loading of the helicase by DnaC. The helicase unwinds DNA, and two replication forks are established that proceed bidirectionally until termination.

In archaea and eukaryotes, genomes typically contain multiple origins per chromosome. Origin licensing occurs during G1: the origin recognition complex (ORC) binds origins and, with Cdc6 and Cdt1, loads the MCM2-7 helicase. Activation in S phase, driven by S-phase kinases (CDK and DDK), converts licensed origins into active firing sites, initiating replication forks. Origin efficiency and timing vary and are influenced by chromatin structure, transcription, and higher-order genome organization.

Origins are defined by function rather than a universal DNA motif; bacterial origins have recognizable sequence elements, while eukaryotic origins are often determined by chromatin context rather than exact sequences. Genome-wide maps of origins rely on nascent-strand sequencing, bubble-seq, and Okazaki fragment sequencing (OK-seq). Mapping reveals replication timing domains and origin firing patterns essential for genome stability.

Proper origin control prevents re-replication and maintains genome integrity. Dysregulation can contribute to genomic instability and cancer. The study of Replikationsorigin encompasses molecular initiators, licensing and firing mechanisms, replication timing, and interactions with chromatin and nuclear architecture.