[Mechanisms of repair and radiation-induced mutagenesis in higher eukaryotes].
Cells of higher eukaryotes possess several very efficient systems for the repair of radiation-induced lesions in DNA. Different strategies have been adopted at the cellular level to remove or even tolerate various types of lesions in order to assure survival and limit the mutagenic consequences. In mammalian cells, the main DNA repair systems comprise direct reversion of damage, excision of damage and exchange mechanisms with intact DNA. Among these, the direct ligation of single strand breaks (SSB) by a DNA ligase and the multi-enzymatic repair systems of mismatch repair, base and nucleotide excision repair as well as the repair of double strand breaks (DSB) by homologous recombination or non homologous end-joining are the most important systems. Most of these processes are error-free except the non homologous end-joining pathway used mainly for the repair of DSB. Moreover, certain lesions can be tolerated by more or less accurately acting polymerases capable of performing translesional DNA syntheses. The DNA repair systems are intimately integrated in the network of cellular regulation. Some of their components are DNA damage inducible. Radiation-induced mutagenesis is largely due to unrepaired DNA damage but also involves error-prone repair processes like the repair of DSB by non-homologous end-joining. Generally, mammalian cells are well prepared to repair radiation-induced lesions. However, some questions remain to be asked about mechanistic details and efficiencies of the systems for removing certain types of radiation-damage and about their order and timing of action. The answers to these questions would be important for radioprotection as well as radiotherapy.
Averbeck
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Institut Curie, laboratoires Raymond-Latarjet, UMR2027 CNRS, centre universitaire d'Orsay, France.
D000818:Animals; D004247:DNA / Q000528:radiation effects*; D004249:DNA Damage / Q000502:physiology; D004260:DNA Repair / Q000502:physiology*; D005057:Eukaryotic Cells / Q000528:radiation effects*; D006801:Humans; D016296:Mutagenesis / Q000528:radiation effects*
D004247:DNA