DNA is the carrier of the genetic information that defines every living being. The genetic code defined in the DNA is an essential part of processes from the subcellular level to the appearance and function of the organism as a whole. Nevertheless, DNA is at risk from endogenous sources such as hydrolysis, oxidation, alkylation or replication errors. In addition, there is ionizing radiation, UV radiation and a number of chemical reagents that form external risk factors for the integrity of the DNA.
Unlike RNA and proteins, DNA is not broken down and synthesized as a result of damage. Instead, there are numerous repair signaling pathways that ensure that the DNA remains intact. Francis Crick noted in 1974 that “we completely ignored the possible role of enzymes in [DNA] repair. It was only later that I discovered that the DNA is so valuable that several separate mechanisms could be involved. ”
This premonition has been confirmed: Since then, more than 100 genes have been identified that are involved in the complex network of DNA repair signaling pathways. Depending on the type of lesion, DNA damage can be repaired using six different signaling pathways: chemical modification, nucleotide incorrect installation and cross-linking are remedied by direct repair (DR), mismatch repair (MMR) or nucleotide excision repair. Single-strand breaks in DNA are repaired by base excision, and highly mutagenic double-strand breaks are finally repaired by a series of complex signaling pathways based on homologous recombination (HR) with the sister chromatid (in the S or G2 phase of the cell cycle) or the non-homologous end linkage (non-homologous end-joining, NHEJ). In the event that a DNA lesion cannot be repaired in time, special DNA polymerases enable translational synthesis (TLS), which prevents the delay in the DNA replication fork. Mutations that disable parts of these repair signaling pathways can trigger diseases such as Xeroderma pigmentosum, Louis Bar syndrome, Fanconi anemia and a predisposition to cancer.
Furthermore, these repair mechanisms are of great interest for the approach of targeted genome editing, which makes use of the cellular DNA repair mechanisms.