title: The Arabidopsis SIAMESE-RELATED cyclin-dependent kinase inhibitors SMR5 and SMR7 regulate the DNA damage checkpoint in response to reactive oxygen species.
abstract: Whereas our knowledge about the diverse pathways aiding DNA repair upon genome damage is steadily increasing, little is known about the molecular players that adjust the plant cell cycle in response to DNA stress. By a meta-analysis of DNA stress microarray data sets, three family members of the SIAMESE/SIAMESE-RELATED (SIM/SMR) class of cyclin-dependent kinase inhibitors were discovered that react strongly to genotoxicity. Transcriptional reporter constructs corroborated specific and strong activation of the three SIM/SMR genes in the meristems upon DNA stress, whereas overexpression analysis confirmed their cell cycle inhibitory potential. In agreement with being checkpoint regulators, SMR5 and SMR7 knockout plants displayed an impaired checkpoint in leaf cells upon treatment with the replication inhibitory drug hydroxyurea (HU). Surprisingly, HU-induced SMR5/SMR7 expression depends on ATAXIA TELANGIECTASIA MUTATED (ATM) and SUPPRESSOR OF GAMMA RESPONSE1, rather than on the anticipated replication stress-activated ATM AND RAD3-RELATED kinase. This apparent discrepancy was explained by demonstrating that, in addition to its effect on replication, HU triggers the formation of reactive oxygen species (ROS). ROS-dependent transcriptional activation of the SMR genes was confirmed by different ROS-inducing conditions, including high-light treatment. We conclude that the identified SMR genes are part of a signaling cascade that induces a cell cycle checkpoint in response to ROS-induced DNA damage.
authors.affiliation: Department of Plant Systems Biology, VIB, B-9052 Gent, Belgium.
authors.forename: Dalong
authors.initials: D
authors.lastname: Yi
authors.forename: Claire Lessa
authors.initials: CL
authors.lastname: Alvim Kamei
authors.forename: Toon
authors.initials: T
authors.lastname: Cools
authors.forename: Sandy
authors.initials: S
authors.lastname: Vanderauwera
authors.forename: Naoki
authors.initials: N
authors.lastname: Takahashi
authors.forename: Yoko
authors.initials: Y
authors.lastname: Okushima
authors.forename: Thomas
authors.initials: T
authors.lastname: Eekhout
authors.forename: Kaoru Okamoto
authors.initials: KO
authors.lastname: Yoshiyama
authors.forename: John
authors.initials: J
authors.lastname: Larkin
authors.forename: Hilde
authors.initials: H
authors.lastname: Van den Daele
authors.forename: Phillip
authors.initials: P
authors.lastname: Conklin
authors.forename: Anne
authors.initials: A
authors.lastname: Britt
authors.forename: Masaaki
authors.initials: M
authors.lastname: Umeda
authors.forename: Lieven
authors.initials: L
authors.lastname: De Veylder
mesh_terms: D017360:Arabidopsis / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D029681:Arabidopsis Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D059447:Cell Cycle Checkpoints; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D050756:Cyclin-Dependent Kinase Inhibitor Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004249:DNA Damage; D018506:Gene Expression Regulation, Plant; D055786:Gene Knockout Techniques; D006918:Hydroxyurea / Q000494:pharmacology; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000494:pharmacology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology
chemical_list: D029681:Arabidopsis Proteins; D018797:Cell Cycle Proteins; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D017382:Reactive Oxygen Species; C000592968:SMR5 protein, Arabidopsis; C561308:SOG1 protein, Arabidopsis; D014157:Transcription Factors; D006918:Hydroxyurea