Translesion replication

Abstract Translesion replication (TR) is a specialized form of DNA replication that is used to extend nascent chains past sites of unrepaired template damage that would otherwise impede or block elongation. The progress of replication forks can be inhibited by a wide variety of DNA lesions, including UV photoproducts, chemical adducts, and abasic sites. They are sometimes collectively called ‘bulky’ lesions because each appreciably alters DNA structure. Translesion replication therefore enhances the ability of cells to tolerate DNA damage, and increases survival when their genomes contain unrepaired damage. On occasion, it is called ‘error-prone repair’, but this is a less suitable name because translesion replication does not itself repair DNA, though it does produce molecules that are substrates for repair by other processes. Although TR increases tolerance to DNA damage, it is also a major source of both spontaneous and induced mutations, which are rarely beneficial. Mutations arise principally because the accuracy with which DNA polymerases insert the correct number or type of nucleotide opposite a site of template damage is usually much lower than is typically found for replication on undamaged templates, though some mutations may also arise because of the lower inherent accuracy of the DNA polymerase employed in TR. Nevertheless, TR still favours survival, since its error frequency rarely approaches 100%, and moreover many mutations are essentially neutral.