title: ATR cooperates with CTC1 and STN1 to maintain telomeres and genome integrity in Arabidopsis.
abstract: The CTC1/STN1/TEN1 (CST) complex is an essential constituent of plant and vertebrate telomeres. Here we show that CST and ATR (ataxia telangiectasia mutated [ATM] and Rad3-related) act synergistically to maintain telomere length and genome stability in Arabidopsis. Inactivation of ATR, but not ATM, temporarily rescued severe morphological phenotypes associated with ctc1 or stn1. Unexpectedly, telomere shortening accelerated in plants lacking CST and ATR. In first-generation (G1) ctc1 atr mutants, enhanced telomere attrition was modest, but in G2 ctc1 atr, telomeres shortened precipitously, and this loss coincided with a dramatic decrease in telomerase activity in G2 atr mutants. Zeocin treatment also triggered a reduction in telomerase activity, suggesting that the prolonged absence of ATR leads to a hitherto-unrecognized DNA damage response (DDR). Finally, our data indicate that ATR modulates DDR in CST mutants by limiting chromosome fusions and transcription of DNA repair genes and also by promoting programmed cell death in stem cells. We conclude that the absence of CST in Arabidopsis triggers a multifaceted ATR-dependent response to facilitate maintenance of critically shortened telomeres and eliminate cells with severe telomere dysfunction.
authors.affiliation: Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX 77843, USA.
authors.forename: Kara A
authors.initials: KA
authors.lastname: Boltz
authors.forename: Katherine
authors.initials: K
authors.lastname: Leehy
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Song
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Nelson
authors.forename: Dorothy E
authors.initials: DE
authors.lastname: Shippen
mesh_terms: D017360:Arabidopsis / Q000235:genetics / Q000378:metabolism; D029681:Arabidopsis Proteins / Q000235:genetics* / Q000378:metabolism*; D064007:Ataxia Telangiectasia Mutated Proteins; D001761:Bleomycin / Q000494:pharmacology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D004260:DNA Repair; D016678:Genome; D042822:Genomic Instability; D005838:Genotype; D030821:Plants, Genetically Modified; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism*; D019098:Telomerase / Q000378:metabolism; D016615:Telomere / Q000502:physiology; D059505:Telomere Homeostasis; D059506:Telomere Shortening; D034501:Telomere-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D029681:Arabidopsis Proteins; C544991:CTC1 protein, Arabidopsis; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; C534225:STN1 protein, Arabidopsis; D034501:Telomere-Binding Proteins; D001761:Bleomycin; C105427:Zeocin; C576892:ATR protein, Arabidopsis; D064007:Ataxia Telangiectasia Mutated Proteins; C568260:CAST AWAY protein, Arabidopsis; D017346:Protein Serine-Threonine Kinases; D019098:Telomerase