title: Repair of DNA Damage Induced by the Cytidine Analog Zebularine Requires ATR and ATM in Arabidopsis.
abstract: DNA damage repair is an essential cellular mechanism that maintains genome stability. Here, we show that the nonmethylable cytidine analog zebularine induces a DNA damage response in Arabidopsis thaliana, independent of changes in DNA methylation. In contrast to genotoxic agents that induce damage in a cell cycle stage-independent manner, zebularine induces damage specifically during strand synthesis in DNA replication. The signaling of this damage is mediated by additive activity of ATAXIA TELANGIECTASIA MUTATED AND RAD3-RELATED and ATAXIA TELANGIECTASIA MUTATED kinases, which cause postreplicative cell cycle arrest and increased endoreplication. The repair requires a functional STRUCTURAL MAINTENANCE OF CHROMOSOMES5 (SMC5)-SMC6 complex and is accomplished predominantly by synthesis-dependent strand-annealing homologous recombination. Here, we provide insight into the response mechanism for coping with the genotoxic effects of zebularine and identify several components of the zebularine-induced DNA damage repair pathway.
authors.affiliation: Department of Plant Breeding and Genetics, Max Planck Institute for Plant Breeding Research, 50829 Cologne, Germany.
authors.forename: Chun-Hsin
authors.initials: CH
authors.lastname: Liu
authors.affiliation: Department of Plant Breeding and Genetics, Max Planck Institute for Plant Breeding Research, 50829 Cologne, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Finke
authors.affiliation: Department of Plant Breeding and Genetics, Max Planck Institute for Plant Breeding Research, 50829 Cologne, Germany.
authors.forename: Mariana
authors.initials: M
authors.lastname: Díaz
authors.affiliation: Biotechnology of Horticultural Crops, Technische Universität München, 85354 Freising, Germany.
authors.forename: Wilfried
authors.initials: W
authors.lastname: Rozhon
authors.affiliation: Biotechnology of Horticultural Crops, Technische Universität München, 85354 Freising, Germany.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Poppenberger
authors.affiliation: University of Zürich, 8057 Zürich, Switzerland.
authors.forename: Tuncay
authors.identifier: http://orcid.org/0000-0001-8474-6587
authors.initials: T
authors.lastname: Baubec
authors.affiliation: Department of Plant Breeding and Genetics, Max Planck Institute for Plant Breeding Research, 50829 Cologne, Germany pecinka@mpipz.mpg.de.
authors.forename: Ales
authors.initials: A
authors.lastname: Pecinka
mesh_terms: D017360:Arabidopsis / Q000235:genetics / Q000502:physiology*; D029681:Arabidopsis Proteins / Q000502:physiology; D064007:Ataxia Telangiectasia Mutated Proteins / Q000502:physiology*; D002453:Cell Cycle / Q000187:drug effects; D003562:Cytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004249:DNA Damage / Q000187:drug effects*; D004260:DNA Repair / Q000502:physiology*; D004261:DNA Replication / Q000187:drug effects
chemical_list: C576589:ATM protein, Arabidopsis; D029681:Arabidopsis Proteins; D003562:Cytidine; C009131:pyrimidin-2-one beta-ribofuranoside; C576892:ATR protein, Arabidopsis; D064007:Ataxia Telangiectasia Mutated Proteins