ORC1

ORC1, or Origin Recognition Complex subunit 1, is a protein encoded by the ORC1 gene and is the largest subunit of the origin recognition complex (ORC) in eukaryotes. It is a core component of the six-subunit ORC that binds replication origins to license DNA replication.

Its primary function is origin licensing: the ORC complex binds origins during G1 phase and, with CDC6 and CDT1, recruits the MCM2-7 helicase to DNA, enabling the formation of the pre-replicative complex and preparation for DNA synthesis in S phase. ORC1 participates in assembling this licensing machinery and interacts with other ORC subunits as well as licensing factors to ensure origins are properly prepared for replication.

Structural features of ORC1 include conserved domains such as an AAA+ ATPase domain, which is implicated in nucleotide binding and hydrolysis, and a BAH (bromo-adjacent homology) domain that contributes to chromatin interactions and protein–DNA binding. The protein's activity and chromatin association are tightly regulated during the cell cycle and are subject to post-translational modifications, including phosphorylation and ubiquitin-mediated degradation, to prevent re-replication of DNA.

In addition to its canonical role in licensing, ORC1 has been reported to participate in related processes such as centrosome duplication and chromatin organization in some systems, though these roles require further clarification.

Mutations in ORC1 have been associated with Meier-Gorlin syndrome, a form of primordial dwarfism, reflecting the essential nature of origin licensing for normal development. The function and regulation of ORC1 are conserved across eukaryotes, with studies in model organisms contributing to understanding of replication origin licensing and cell-cycle control.