Cell Cycle Control and DNA Damage Signaling in Mammals
Normal cellular functions, development, and disease prevention depend on genome stability maintenance. To safeguard the accurate transmission of genetic information, mammalian cells utilize cell cycle mechanisms coordinating DNA replication and mitosis. Upon DNA damage, diverse pathways are activated to promote cell cycle arrest and DNA damage repair. Collectively, these pathways are known as the DNA damage response, the major guardian of genomic integrity. The activation of DNA damage induced cell cycle checkpoints (termed DNA damage checkpoints) allows the completion of DNA repair before cell cycle progression continues. In case the DNA damage is beyond repair, the damaged cell commits to apoptosis or senescence. Here, we summarize the regulation of the mammalian cell cycle in the context of DNA damage signaling and DNA damage repair mechanisms. Since DNA damage checkpoints can prevent cancer development and influence somatic and stem cell physiology, we also discuss some molecular aspects in the context of disease.