- Endoreduplication is a specialised cell‑cycle programme in which cells replicate their DNA repeatedly without entering mitosis or undergoing cytokinesis. Because mitosis is skipped, each round of replication increases the nuclear DNA content, producing polyploid cells with 4N, 8N, 16N or even higher genome copies. This process is common in plants, insects and certain mammalian tissues, and it plays important roles in growth, differentiation and stress tolerance. Unlike uncontrolled polyploidy seen in disease, endoreduplication is a regulated developmental strategy that enhances cellular capacity.
- In a normal mitotic cycle, cells progress through G1, S, G2 and M phases. Endoreduplication modifies this pattern by alternating only between G and S phases. The cell replicates its DNA, returns to a gap phase, and then re‑enters S phase without ever activating the mitotic machinery. This requires precise suppression of mitotic cyclin‑dependent kinase (CDK) activity. Mitotic drivers such as CDK1 and Cyclin B remain inactive, while S‑phase regulators including Cyclin E, Cyclin A and CDK2 continue to function. The anaphase‑promoting complex APC/C, particularly in association with Cdh1, helps maintain low mitotic cyclin levels, ensuring that the cell does not initiate mitosis. Transcriptional repressors such as E2F7/E2F8 further silence mitotic genes, reinforcing the endocycle state.
- Endoreduplication serves several biological purposes. In plants, it is a major driver of cell enlargement and metabolic output, supporting rapid tissue growth in leaves, fruits and endosperm. In insects such as Drosophila, salivary gland cells undergo dramatic endoreduplication to form polytene chromosomes, enabling extremely high transcriptional activity. In mammals, hepatocytes, megakaryocytes and trophoblast giant cells use endoreduplication to increase biosynthetic capacity, support detoxification, produce platelets or sustain placental development. Polyploid cells generated through endoreduplication often show enhanced resilience to DNA damage and oxidative stress, making this process beneficial under demanding physiological conditions.
- Although endoreduplication is normally a controlled developmental programme, its dysregulation can contribute to disease. In cancer, aberrant polyploidisation may arise when mitotic checkpoints fail or when DNA damage forces cells into an endocycle‑like state. Polyploid tumour cells often resist apoptosis, survive chemotherapy and generate genetically unstable progeny that promote tumour progression. However, this pathological polyploidy differs from the regulated endoreduplication seen in healthy tissues.
- Overall, endoreduplication is a remarkable variation of the cell cycle that allows cells to increase their genomic content and functional capacity without division. By suppressing mitosis and sustaining S‑phase activity, cells can grow larger, produce more proteins and adapt to developmental or environmental demands. Its study provides important insights into development, regeneration and the mechanisms by which cells alter their cell‑cycle programmes.
