DNA-damage tolerance through PCNA ubiquitination and sumoylation.

摘要: DNA-damage tolerance (DDT) is employed by eukaryotic cells to bypass replication-blocking lesions induced DNA-damaging agents. In budding yeast Saccharomyces cerevisiae, DDT mediated RAD6 epistatic group genes and the central event for sequential ubiquitination of proliferating cell nuclear antigen (PCNA), a DNA clamp required replication repair. consists two parallel pathways: error-prone PCNA monoubiquitination, which recruits translesion synthesis polymerases with decreased fidelity; error-free K63-linked polyubiquitination at same residue facilitates homologous recombination-mediated template switch. Interestingly, also subjected sumoylation, leads inhibition unwanted recombination forks. All three types posttranslational modifications require dedicated conjugating ligation enzymes, these enzymes are highly conserved in eukaryotes, from human.