ORC3 Antibody

Definition and Target Specificity

ORC3 antibodies are monoclonal or polyclonal reagents designed to detect the ORC3 protein, a 62 kDa subunit of the heterohexameric Origin Recognition Complex (ORC). ORC binds replication origins in an ATP-dependent manner and recruits factors like Cdc6 and MCM helicase to form pre-replicative complexes . Key features of ORC3 antibodies include:

• Epitope specificity: Targets regions such as the N-terminal (AA 17–46) or full-length ORC3 .

• Species reactivity: Primarily validated in humans .

• Applications: Western blot (WB), immunoprecipitation (IP), immunohistochemistry (IHC), and chromatin immunoprecipitation (ChIP) .

Role in DNA Replication and Chromatin Dynamics

• ORC3 interacts with trimethylated histone H3K4 via Spp1p (a Set1 complex member), linking replication machinery to epigenetic regulation .

  • orc2-1 mutants showed reduced H3K4 trimethylation, suggesting ORC’s role in chromatin remodeling .

• ORC3 localizes to replication origins but also exhibits non-nuclear roles, such as cytoplasmic puncta in hippocampal neurons, influencing dendritic growth and spine development .

  • Knockdown of orc3 reduced dendritic branchpoints by 35–57% and spine density by 76–78% .

Clinical and Translational Relevance

• Cancer Research: ORC3 is overexpressed in lung adenocarcinoma (LUAD), correlating with poor prognosis .

  • High ORC3 mRNA/protein levels in tumors vs. normal tissues suggest oncogenic potential .

• Neurological Disorders: ORC3’s cytoplasmic role in dendrite morphogenesis highlights its implications in neurodevelopmental pathologies .

Functional Assays and Protocols

Key Challenges and Future Directions

• Specificity: ORC antibodies may cross-react with non-origin DNA due to limited sequence discrimination .

• Therapeutic Potential: Targeting ORC3 in cancers requires deeper mechanistic insights into replication dysregulation .