Multiple functions of the origin recognition complex.

Abstract

The origin recognition complex (ORC), a heteromeric six-subunit protein, is a central component for eukaryotic DNA replication. The ORC binds to DNA at replication origin sites in an ATP-dependent manner and serves as a scaffold for the assembly of other key initiation factors. Sequence rules for ORC-DNA binding appear to vary widely. In budding yeast the ORC recognizes specific ori elements, however, in higher eukaryotes origin site selection does not appear to depend on the specific DNA sequence. In metazoans, during cell cycle progression, one or more of the ORC subunits can be modified in such a way that ORC activity is inhibited until mitosis is complete and a nuclear membrane is assembled. In addition to its well-documented role in the initiation of DNA replication, the ORC is also involved in other cell functions. Some of these activities directly link cell cycle progression with DNA replication, while other functions seem distinct from replication. The function of ORCs in the establishment of transcriptionally repressed regions is described for many species and may be a conserved feature common for both unicellular eukaryotes and metazoans. ORC subunits were found at centrosomes, at the cell membranes, at the cytokinesis furrows of dividing cells, as well as at the kinetochore. The exact mechanism of these localizations remains to be determined, however, latest results support the idea that ORC proteins participate in multiple aspects of the chromosome inheritance cycle. In this review, we discuss the participation of ORC proteins in various cell functions, in addition to the canonical role of ORC in initiating DNA replication.