- Borealin (also known as CDCA8) is a core component of the Chromosomal Passenger Complex (CPC), functioning alongside Aurora B kinase, INCENP and Survivin. While Aurora B provides catalytic activity and INCENP acts as the scaffold, Borealin is the structural stabiliser that anchors the CPC to chromatin, ensures correct centromere localisation and maintains complex integrity throughout mitosis. Without Borealin, the CPC collapses, Aurora B becomes mis‑localised, and cells fail to execute accurate chromosome segregation.
- Borealin’s N‑terminal region forms a three‑helix bundle with Survivin and INCENP. This trimeric subcomplex is essential for targeting the CPC to the inner centromere during prometaphase and metaphase. Borealin’s contribution is structural: it stabilises the interaction surface, prevents premature dissociation and ensures that Aurora B is positioned correctly to monitor kinetochore–microtubule attachments.
- The C‑terminal region of Borealin contains a flexible domain that interacts with chromatin and regulatory proteins. This region is required for CPC retention at centromeres and for the transition of the complex to the spindle midzone during anaphase. Borealin’s chromatin‑binding ability is crucial for CPC dynamics—without it, Aurora B cannot relocate properly, leading to defects in spindle midzone formation and cytokinesis.
- Borealin also plays a role in error correction. By stabilising CPC localisation at centromeres, Borealin ensures that Aurora B can phosphorylate kinetochore substrates such as Ndc80, KNL1 and MCAK. This phosphorylation destabilises incorrect microtubule attachments, allowing cells to achieve proper bi‑orientation. Borealin therefore indirectly prevents aneuploidy and maintains genomic stability.
- During anaphase, Borealin participates in CPC relocation to the central spindle. This movement is regulated by phosphorylation events and interactions with microtubule‑associated proteins. At the midbody, Borealin supports Aurora B’s role in cytokinesis, ensuring proper contractile ring formation and membrane abscission.
- Borealin is frequently overexpressed in cancers, including colorectal, breast and hepatocellular carcinoma. Its overexpression correlates with chromosomal instability, high proliferation rates and poor prognosis. Because Borealin is essential for CPC stability, targeting Borealin or its interactions is being explored as a strategy to disrupt mitosis selectively in tumour cells.
- In summary, Borealin is the structural anchor of the CPC, stabilising the complex, ensuring centromere localisation, supporting Aurora B activity and enabling CPC movement across mitosis. Its roles in chromosome segregation, error correction and cytokinesis make Borealin indispensable for mitotic fidelity and a significant factor in cancer biology.
