Figure 1. The principal elements of eukaryotic deoxyribonucleic acid (DNA) replication origins (ori). The minimal ori or ‘core’ element consists of: a DNA unwinding element (DUE) that is easily unwound; an origin recognition element (ORE), which is bound by the initiator protein(s) (IPs), including the Ku protein; an AT-rich sequence (AT), where DNA bending occurs and an inverted repeat (IR) sequence that has the potential of extruding into a cruciform conformation and as such is bound by a cruciform-binding protein (CBP), which in human cells was identified as belonging to the 14-3-3 protein family. The position of the AT and DUE elements with respect to ORE and IR elements indicates only their inclusion within a predicted core. The core element is flanked by the auxiliary components (Aux), which are binding sites of transcription factors that are specific to particular replication systems and influence the initiation of DNA replication, through their interaction with origin-binding proteins and other replication proteins. (Adapted from DePamphilis ML (1993) Annual Review of Biochemistry 62: 29–63, and based on data regarding mammalian replication oris, described by Novac et al., 2002, 2001).