Orc1, the largest subunit of the origin recognition complex, is crucial for DNA replication initiation. It is involved in pathways related to cell cycle regulation and chromatin-associated processes, being of great biological importance in organisms from archaea to eukaryotes [1,2,3,4,6]. Genetic models are valuable for studying its functions.

In human cells, ORC1 binds to cis-transcribed RNAs at transcription start sites of genes with origins, and RNA binding is essential for efficient activation of proximal origins, as RNA depletion or using ORC1 RNA-binding mutants leads to impaired ORC1 chromatin release [2]. In HIV-1 latency, ORC1 is enriched on the HIV-1 promoter, recruiting repressive epigenetic elements to promote latency, and its depletion reactivates latent HIV-1 in various latency cell models and primary CD4+ T cells [3]. In cancer, ORC1 is highly expressed in most tumors, associated with pathological stages and prognosis in some cancer types, and may inhibit tumor immunity, making it a potential biomarker and therapeutic target [5].

In conclusion, Orc1 is vital for DNA replication initiation and also plays significant roles in processes like replication origin activation, HIV-1 latency, and cancer. Studies using various models, though not specifically KO/CKO mouse models in the provided references, have enhanced our understanding of its functions in these biological processes and disease conditions, which may guide future research in developing treatments for related diseases.