DNA-damage tolerance through PCNA ubiquitination and sumoylation. Issue 14 (29th July 2020)

• Record Type: Journal Article
• Authors: Fan, Li; Bi, Tonghui; Wang, Linxiao; Xiao, Wei
• Is Part Of: Biochemical journal. Volume 477:Issue 14(2020)
• Page Start: 2655
• Page End: 2677
• Publication Date: 2020-07-29
• Subjects: DNA-damage tolerance -- PCNA -- schizosaccharomyces pombemyces -- sumoylation -- ubiquitins; Biochemistry -- Periodicals; 572
• DOI: 10.1042/BCJ20190579
• Languages: English
• ISSNs: 0264-6021

Abstract

Abstract : 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.