Cellular Responses to DNA Damage

Genomic integrity is central to cellular survival, yet all organisms sustain a certain number of background mutations as a result of numerous stressors, cellular processes, or interactions with the environment, coupled with limited DNA chemical stability. To counteract steady-state DNA damage load from endogenous and exogenous stressors, cells have evolved biological processes to reduce the biological consequences of DNA damage, including DNA repair systems, DNA damage response and damage tolerance pathways. These pathways are highly conserved and ubiquitous, and are found in bacteria, plants, and eukaryotes. Major DNA repair pathways include direct repair, base excision repair, nucleotide excision repair, mismatch repair, and double strand break repair pathways. While the repair systems are tailored to the specific kinds of damage, there is considerable overlap between their substrates. The complex interactions between the different DNA repair, tolerance and damage response pathways counteract the effects of ever-present background DNA damage in cells, prevent mutagenic outcomes and reflect the very low level of spontaneous mutagenesis. The interactions of various DNA repair and DNA damage response pathways also provide the biological basis for mutational thresholds from the low-dose exposures to exogenous, DNA reactive agents.