Cancer arises from uncontrolled cell growth and genomic instability, often due to defective checkpoints and DNA repair mechanisms. Claspin is a key regulator in this process, acting as a scaffold protein that activates the ATR-Chk1 checkpoint in response to DNA damage or replication stress. By pausing the cell cycle, Claspin allows DNA repair or triggers apoptosis, while also stabilizing replication forks and coordinating DNA synthesis. It links checkpoint activation to repair pathways like homologous recombination and the FANC/BRCA network, and even contributes to epigenetic regulation.
Claspin has a dual role in cancer. As a tumor suppressor, its loss or degradation—sometimes exploited by viruses like HPV and EBV—can drive malignant transformation, with low CLSPN expression often correlating with poor prognosis. Conversely, in certain cancers, Claspin acts as an oncogene, supporting DNA repair and replication to enhance tumor survival and therapy resistance.
Because of its central role in DNA damage response, Claspin contributes to chemotherapy and radiation resistance. Targeting Claspin or its pathways offers a promising approach to sensitize tumors and improve treatment outcomes.