title: Arabidopsis ATM and ATR kinases prevent propagation of genome damage caused by telomere dysfunction.
abstract: The ends of linear eukaryotic chromosomes are hidden in nucleoprotein structures called telomeres, and loss of the telomere structure causes inappropriate repair, leading to severe karyotypic and genomic instability. Although it has been shown that DNA damaging agents activate a DNA damage response (DDR), little is known about the signaling of dysfunctional plant telomeres. We show that absence of telomerase in Arabidopsis thaliana elicits an ATAXIA-TELANGIECTASIA MUTATED (ATM) and ATM AND RAD3-RELATED (ATR)-dependent DDR at telomeres, principally through ATM. By contrast, telomere dysfunction induces an ATR-dependent response in telomeric Conserved telomere maintenance component1 (Ctc1)-Suppressor of cdc thirteen (Stn1)-Telomeric pathways in association with Stn1 (CST)-complex mutants. These results uncover a new role for the CST complex in repressing the ATR-dependent DDR pathway in plant cells and show that plant cells use two different DNA damage surveillance pathways to signal telomere dysfunction. The absence of either ATM or ATR in ctc1 and stn1 mutants significantly enhances developmental and genome instability while reducing stem cell death. These data thus give a clear illustration of the action of ATM/ATR-dependent programmed cell death in maintaining genomic integrity through elimination of genetically unstable cells.
authors.affiliation: Génétique, Reproduction et Développement, Unité Mixte de Recherche Centre National de la Recherche Scientifique 6247, Clermont Université, Institut National de la Santé et de la Recherche Médicale U931, Aubiere, France.
authors.forename: Simon
authors.initials: S
authors.lastname: Amiard
authors.forename: Annie
authors.initials: A
authors.lastname: Depeiges
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Allain
authors.forename: Charles I
authors.initials: CI
authors.lastname: White
authors.forename: Maria Eugenia
authors.initials: ME
authors.lastname: Gallego
mesh_terms: D017360:Arabidopsis / Q000201:enzymology / Q000235:genetics*; D029681:Arabidopsis Proteins / Q000235:genetics* / Q000378:metabolism; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D016923:Cell Death; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism; D032461:Chromosomes, Plant / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D004789:Enzyme Activation; D018745:Genome, Plant; D042822:Genomic Instability; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D059828:Plant Cells / Q000378:metabolism; D018517:Plant Roots / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D016615:Telomere / Q000235:genetics* / Q000378:metabolism; D059505:Telomere Homeostasis; D034501:Telomere-Binding Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D029681:Arabidopsis Proteins; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D034501:Telomere-Binding Proteins; C576589:ATM protein, Arabidopsis; C544991:CTC1 protein, Arabidopsis; C534225:STN1 protein, Arabidopsis; C576892:ATR protein, Arabidopsis