Abstract
Cell cycle checkpoints are a regulatory mechanism that prevents transition of cells into subsequent phases until all processes in the previous phase are completed, ensuring genomic integrity. Arrest in G1 is considered to prevent aberrant replication of damaged DNA and arrest in G2 allows cells to avoid segregation of defective chromosomes. Therefore, defective cell cycle checkpoints lead to gene mutations and chromosome damage which contribute to tumorigenesis. However, recent observations indicate that loss of checkpoint function in cancer cells is associated with their sensitivity to antineoplastic treatments such as chemotherapy and radiation. By treatment with those genotoxic agents, cancer cells having impairment of checkpoint functions initially arrest in the G2 phase of the cell cycle but are unable to maintain cell-cycle arrest. Those cells eventually die as they enter mitosis. This process is referred to as ‘mitotic catastrophe’. In this review, we propose the critical relationship between checkpoint functions and sensitivity of cancer cells to anti-tumor therapies. [Skin Cancer (Japan) 2004; 19: 281-286]
