title: Error-free DNA-damage tolerance in Saccharomyces cerevisiae.
abstract: DNA-damage tolerance (DDT) is an important mechanism for living cells to bypass replication blocks on the template strand. In Saccharomyces cerevisiae, DDT is mediated by the RAD6 epistasis group of genes, consisting of two parallel pathways: error-prone translesion DNA synthesis (TLS), and error-free lesion bypass. The two pathways are activated by sequential ubiquitination of PCNA on the Lys164 residue. When a replication fork is stalled at a lesion, PCNA is first monoubiquitinated by Rad6-Rad18, which leads to the TLS pathway. The subsequent ubiquitination by the Mms2-Ubc13-Rad5 complex on the monoubiquitinated PCNA is to form a Lys63-linked polyubiquitin chain that promotes error-free lesion bypass. While the TLS pathway has been extensively characterized, the molecular events leading to error-free lesion bypass by polyubiquitinated PCNA are largely obscure. Furthermore, PCNA can also be sumoylated at the same Lys164 residue, which helps to recruit Srs2, a helicase and anti-recombinase. This review summarizes recent advances in our understanding of error-free DDT and its interplay with Srs2 and homologous recombination.
authors.affiliation: College of Life Sciences, Capital Normal University, Beijing, 100048, China; Department of Microbiology and Immunology, University of Saskatchewan, Saskatoon, SK, Canada.
authors.forename: Xin
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Microbiology and Immunology, University of Saskatchewan, Saskatoon, SK, Canada.
authors.forename: Susan
authors.initials: S
authors.lastname: Blackwell
authors.affiliation: College of Life Sciences, Capital Normal University, Beijing, 100048, China.
authors.forename: Aiyang
authors.initials: A
authors.lastname: Lin
authors.affiliation: College of Life Sciences, Capital Normal University, Beijing, 100048, China.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Li
authors.affiliation: College of Life Sciences, Capital Normal University, Beijing, 100048, China.
authors.forename: Zhoushuai
authors.initials: Z
authors.lastname: Qin
authors.affiliation: College of Life Sciences, Capital Normal University, Beijing, 100048, China; Department of Microbiology and Immunology, University of Saskatchewan, Saskatoon, SK, Canada. Electronic address: wei.xiao@usask.ca.
authors.forename: Wei
authors.initials: W
authors.lastname: Xiao
mesh_terms: D004249:DNA Damage; D004265:DNA Helicases / Q000378:metabolism*; D004261:DNA Replication; D004271:DNA, Fungal / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000378:metabolism; D059765:Homologous Recombination; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D058207:Sumoylation; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism
chemical_list: D004271:DNA, Fungal; D004268:DNA-Binding Proteins; C546594:POL30 protein, S cerevisiae; D018809:Proliferating Cell Nuclear Antigen; C063607:RAD18 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C061376:SRS2 protein, S cerevisiae; C471606:RAD6 protein, S cerevisiae; D044763:Ubiquitin-Conjugating Enzymes; D004265:DNA Helicases
keywords: DNA-damage tolerance; Error-free bypass; PCNA; Saccharomyces cerevisiae; Sumoylation; Ubiquitination