title: Polymerases ε and ∂ repair dysfunctional telomeres facilitated by salt.
abstract: Damaged DNA can be repaired by removal and re-synthesis of up to 30 nucleotides during base or nucleotide excision repair. An important question is what happens when many more nucleotides are removed, resulting in long single-stranded DNA (ssDNA) lesions. Such lesions appear on chromosomes during telomere damage, double strand break repair or after the UV damage of stationary phase cells. Here, we show that long single-stranded lesions, formed at dysfunctional telomeres in budding yeast, are re-synthesized when cells are removed from the telomere-damaging environment. This process requires Pol32, an accessory factor of Polymerase δ. However, re-synthesis takes place even when the telomere-damaging conditions persist, in which case the accessory factors of both polymerases δ and ε are required, and surprisingly, salt. Salt added to the medium facilitates the DNA synthesis, independently of the osmotic stress responses. These results provide unexpected insights into the DNA metabolism and challenge the current view on cellular responses to telomere dysfunction.
authors.affiliation: Institute for Cell and Molecular Biosciences (ICaMB), Newcastle University, Newcastle upon Tyne, NE2 44H, UK.
authors.forename: Iglika G
authors.initials: IG
authors.lastname: Ivanova
authors.affiliation: Institute for Cell and Molecular Biosciences (ICaMB), Newcastle University, Newcastle upon Tyne, NE2 44H, UK Laura.Maringele@ncl.ac.uk.
authors.forename: Laura
authors.initials: L
authors.lastname: Maringele
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects; D015825:Chromosomes, Fungal / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D004256:DNA Polymerase I / Q000502:physiology; D004257:DNA Polymerase II / Q000378:metabolism*; D004258:DNA Polymerase III / Q000378:metabolism*; D004260:DNA Repair; D004271:DNA, Fungal / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000378:metabolism; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010692:Phleomycins / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000201:enzymology / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism / Q000502:physiology; D012965:Sodium Chloride / Q000494:pharmacology*; D016615:Telomere / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D059505:Telomere Homeostasis; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D004271:DNA, Fungal; D004268:DNA-Binding Proteins; C081935:MSN2 protein, S cerevisiae; C081937:MSN4 protein, S cerevisiae; D010692:Phleomycins; C522758:Pol32 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D012965:Sodium Chloride; C088589:HOG1 protein, S cerevisiae; D020928:Mitogen-Activated Protein Kinases; D004256:DNA Polymerase I; D004257:DNA Polymerase II; D004258:DNA Polymerase III; D004259:DNA-Directed DNA Polymerase; C083536:POL1 protein, S cerevisiae