Origin recognition complex subunit 1 (ORC1)

Origin recognition complex subunit 1 (ORC1) is the largest component of the hexameric origin recognition complex (ORC), which is essential for the initiation of DNA replication in all eukaryotes. ORC1, encoded by the ORC1 gene, contains a bromo-adjacent homology (BAH) domain and an AAA+ ATPase domain, allowing it to bind origins of replication on DNA and direct assembly of the pre-replication complex by recruiting additional factors such as CDC6, MCM2-7, and Cdt1. ORC1 levels and chromatin binding are tightly regulated across the cell cycle; its phosphorylation status and degradation help coordinate pre-replicative complex formation. In addition to DNA replication, ORC1 interacts with chromatin through histone modifications, contributes to heterochromatin association, and is needed for proper centrosome and centriole duplication. Loss-of-function mutations in ORC1 cause developmental syndromes such as Meier-Gorlin syndrome, emphasizing its essential role in human growth and genome stability. No direct drugs are clinically used to target ORC1, and because it is indispensable for cell proliferation, it is not considered a viable therapeutic target except in rare research contexts.

Other names

ORC1LPARC1HSORC1Replication control protein 1Origin recognition complex, subunit 1 homolog, S. cerevisiae, homolog-like