Cell Cycle/DNA Damage

The repair of DNA lesions that occur endogenously or in response to diverse genotoxic stresses is indispensable for genome integrity. DNA lesions activate checkpoint pathways that regulate specific DNA-repair mechanisms in the different phases of the cell cycle. Checkpoint-arrested cells resume cell-cycle progression once damage has been repaired, whereas cells with unrepairable DNA lesions undergo permanent cell-cycle arrest or apoptosis. Recent studies have provided insights into the mechanisms that contribute to DNA repair in specific cell-cycle phases and have highlighted the mechanisms that ensure cell-cycle progression or arrest in normal and cancerous cells.
The cell cycle consists of four distinct phases: G1 phase, S phase (synthesis), G2 phase and M phase. M phase is itself composed of two tightly coupled processes: karyokinesis, in which the cell's chromosomes are divided, and cytokinesis, in which the cell's cytoplasm divides forming two daughter cells. Activation of each phase is dependent on the proper progression and completion of the previous one. Cells that have temporarily or reversibly stopped dividing are said to have entered a state of quiescence called G0 phase. To combat threats posed by DNA damage, cells have evolved mechanisms to detect DNA lesions, signal their presence and promote their repair. Cells defective in these mechanisms generally display heightened sensitivity towards DNA-damaging agents and, as described further below, many such defects cause human disease.