title: Incision of damaged DNA in the presence of an impaired Smc5/6 complex imperils genome stability.
abstract: The Smc5/6 complex is implicated in homologous recombination-mediated DNA repair during DNA damage or replication stress. Here, we analysed genome-wide replication dynamics in a hypomorphic budding yeast mutant, smc6-P4 The overall replication dynamics in the smc6 mutant is similar to that in the wild-type cells. However, we captured a difference in the replication profile of an early S phase sample in the mutant, prompting the hypothesis that the mutant incorporates ribonucleotides and/or accumulates single-stranded DNA gaps during replication. We tested if inhibiting the ribonucleotide excision repair pathway would exacerbate the smc6 mutant in response to DNA replication stress. Contrary to our expectation, impairment of ribonucleotide excision repair, as well as virtually all other DNA repair pathways, alleviated smc6 mutant's hypersensitivity to induced replication stress. We propose that nucleotide incision in the absence of a functional Smc5/6 complex has more disastrous outcomes than the damage per se Our study provides novel perspectives for the role of the Smc5/6 complex during DNA replication.
authors.affiliation: Department of Biochemistry and Molecular Biology, State University of New York Upstate Medical University, Syracuse, NY 13210, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Peng
authors.affiliation: Department of Biochemistry and Molecular Biology, State University of New York Upstate Medical University, Syracuse, NY 13210, USA fengw@upstate.edu.
authors.forename: Wenyi
authors.identifier: http://orcid.org/0000-0002-6123-7998
authors.initials: W
authors.lastname: Feng
mesh_terms: D000249:Adenosine Monophosphate / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D004249:DNA Damage / Q000187:drug effects; D053843:DNA Mismatch Repair / Q000187:drug effects / Q000235:genetics; D004260:DNA Repair / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects; D004277:DNA, Single-Stranded / Q000235:genetics / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D016681:Genome, Fungal; D042822:Genomic Instability / Q000187:drug effects; D006918:Hydroxyurea / Q000494:pharmacology; D046912:Multiprotein Complexes; D009154:Mutation; D011485:Protein Binding; D016914:Ribonuclease H / Q000378:metabolism; D013312:Stress, Physiological
chemical_list: D018797:Cell Cycle Proteins; D004277:DNA, Single-Stranded; D005656:Fungal Proteins; D046912:Multiprotein Complexes; D000249:Adenosine Monophosphate; C091139:ribonuclease HII; D016914:Ribonuclease H; D006918:Hydroxyurea