ORC1 in health and disease: from DNA replication to cancer

ORC1, the core subunit of the eukaryotic origin recognition complex, plays a critical role in DNA replication initiation, chromatin remodeling, and cell cycle regulation. Under physiological conditions, ORC1 maintains genomic stability by coordinating replication origin licensing, helicase loading, and nucleosome organization, whereas its dysregulation is closely associated with the development and progression of various tumors. ORC1 exhibits context-dependent essentiality in cancer, and targeted strategies such as small-molecule inhibitors are currently under investigation. However, clinical validation of ORC1-directed therapies remains pending, and the current evidence base is predominantly correlative and mechanistic rather than therapeutic. By integrating mechanistic insights with clinical perspectives, this review provides new viewpoints for precision medicine, while highlighting that key issues, including ORC1-independent replication mechanisms, require further investigation.