DNA-damage tolerance through PCNA ubiquitination and sumoylation.

Li Fan, Tonghui Bi, Linxiao Wang, Wei Xiao

The Biochemical journal 2020 Jul 31

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DNA-damage tolerance (DDT) is employed by eukaryotic cells to bypass replication-blocking lesions induced by DNA-damaging agents. In budding yeast Saccharomyces cerevisiae, DDT is mediated by RAD6 epistatic group genes and the central event for DDT is sequential ubiquitination of proliferating cell nuclear antigen (PCNA), a DNA clamp required for replication and DNA repair. DDT consists of two parallel pathways: error-prone DDT is mediated by PCNA monoubiquitination, which recruits translesion synthesis DNA polymerases to bypass lesions with decreased fidelity; and error-free DDT is mediated by K63-linked polyubiquitination of PCNA at the same residue of monoubiquitination, which facilitates homologous recombination-mediated template switch. Interestingly, the same PCNA residue is also subjected to sumoylation, which leads to inhibition of unwanted recombination at replication forks. All three types of PCNA posttranslational modifications require dedicated conjugating and ligation enzymes, and these enzymes are highly conserved in eukaryotes, from yeast to human. © 2020 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Citation

Li Fan, Tonghui Bi, Linxiao Wang, Wei Xiao. DNA-damage tolerance through PCNA ubiquitination and sumoylation. The Biochemical journal. 2020 Jul 31;477(14):2655-2677