ORC3 is a core component of the origin recognition complex (ORC) that plays essential roles in DNA replication initiation and chr6 organization. As part of the ORC, ORC3 participates in ATP-dependent assembly of the pre-replicative complex and MCM2-7 helicase loading at replication origins 1. The protein contains conserved nuclear localization signals and helix-loop-helix motifs that are preserved across eukaryotes 2. ORC3 directly binds to heterochromatin protein 1 (HP1) through both coiled-coil and mod-interacting domains, which are essential for localization to heterochromatic foci 3. This interaction is crucial for HP1 binding to chr6 and maintaining heterochromatin organization 3. During the cell cycle, ORC3 undergoes dynamic regulation, with the complex disassembling during S phase and reassembling through protein phosphatase 1-mediated dephosphorylation of ORC2 in late M phase 4. ORC3 is subject to multi-mono-ubiquitylation by the OBI1 ubiquitin ligase during S phase, which promotes origin firing and CMG complex formation 5. The protein also facilitates MCM2-7 ring closure by recognizing closed ring conformations and interacting with the Mcm5 C-terminus 6. ORC3 expression is constitutively high throughout the cell cycle and shows clinical relevance as a cell cycle progression marker in B-cell precursor acute lymphoblastic leukemia 7.