DNA-DAMAGE AND CELL-CYCLE CHECKPOINTS

DNA is prone to numerous forms of damage that can injure cells and imp air fitness, Cells have evolved an array of mechanisms to repair these injuries, Proliferating cells are especially vulnerable to DNA damage due to the added demands of cellular growth and division. Cell cycle checkpoints represent integral components of DNA repair that coordinat e cooperation between the machinery of the cell cycle and several bioc hemical pathways that respond to damage and restore DNA structure, By delaying progression through the cell cycle, checkpoints provide more time for repair before the critical phases of DNA replication, when th e genome is replicated, and of mitosis, when the genome is segregated, Loss or attenuation of checkpoint function may increase spontaneous a nd induced gene mutations and chromosomal aberrations by reducing the efficiency of DNA repair, Defects in checkpoint control have been seen in certain hereditary cancer syndromes and at early stages of cell tr ansformation, Mutations in checkpoint control genes therefore may cont ribute to the genetic instability that appears to drive neoplastic evo lution.