Cell and tissue responses to genotoxic stress Biology Diagrams Cell cycle checkpoints are critical components of the genotoxic stress response, acting as cellular "quality control" mechanisms. These checkpoints can temporarily halt cell cycle progression, providing time for DNA repair or, in cases of severe damage, initiating programmed cell death. The presented method or slightly modified versions have been devised to study specific treatment responses and side effects of various anti-cancer treatments as used in clinical oncology. It enables a quantitative and longitudinal analysis of the DNA damage response after genotoxic stress, as induce โฆ
For example, upon genotoxic stress, mitochondrial NAD + levels exhibit higher stability than nuclear and cytosolic NAD + pools, which is essential to cell viability 73. Taken together, these results suggest that IRE1ฮฑ deficiency deregulates DDR signaling, thus affecting cell cycle progression, DNA repair and cell survival under genotoxic stress. Genotoxic stress To maintain the integrity of the genome, a cell challenged with genotoxic stress must sense the damage and respond to it by stalling cell cycle progression until the damage is repaired. If the damage is catastrophic, then pro-apoptotic mechanisms are activated, resulting in cell death.
Cell cycle control, checkpoint mechanisms, and genotoxic stress Biology Diagrams
Genotoxic stress leads to DNA damage which can be detrimental to the cell. A well-orchestrated cellular response is mounted to manage and repair the genotoxic stress-induced DNA damage. Our understanding of genotoxic stress response is derived mainly from studies focused on transcription, mRNA splicing, and protein turnover.
In mammalian cells, activation of stress-kinases by genotoxic stress can lead to cell-cycle delay at the G2-M transition, by intersecting with, and activating, the DNA-integrity checkpoints. It is apparent that stress kinases can be activated in an ATM-dependent manner in response to particular genotoxic stresses 52,53. The purpose of this review is to discuss the known signal transduction pathways that regulate cell cycle progression and the mechanisms cells employ to insure DNA stability in the face of genotoxic stress. In particular, we focus on mammalian cell cycle checkpoint functions, their role in maintaining DNA stability during the cell cycle
Proteins from the DNA Damage Response: Regulation, Dysfunction, and ... Biology Diagrams
Abstract Simple Summary. Cells respond to genotoxic stress through complex protein pathways called DNA damage response (DDR). These mechanisms ensure the preservation of genomic integrity and activate DNA repair, cell cycle regulation, and, ultimately, programmed cell death.
