ATR cooperates with CTC1 and STN1 to maintain telomeres and genome integrity in<i>Arabidopsis</i>

Boltz, Kara A.; Leehy, Katherine; Song, Xiangyu; Nelson, Andrew D. L.; Shippen, Dorothy E.

doi:10.1091/mbc.e11-12-1002

Cited by 22 publications

(30 citation statements)

References 78 publications

(154 reference statements)

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“…TER2 expression is unaffected by replication stress or telomere dysfunction, even though DDR is activated in both situations (Boltz et al 2012; this study). Robust telomerase activity would in fact be advantageous in the latter setting, as it could delay the onset of catastrophic telomere failure.…”

Section: Ter2: a Novel Noncoding Rna Induced In Response To Dsbsmentioning

confidence: 49%

“…4F), although both mutations activate DDR ( Fig. 5A; Boltz et al 2012). In plants lacking TERT, all three TER isoforms were reduced, suggesting that TERT promotes their stability.…”

Section: Dna Damage-induced Repression Of Telomerase Activity Correlamentioning

confidence: 89%

“…We recently discovered that telomerase activity is inhibited in A. thaliana seedlings treated with the radiomimetic drug zeocin (Boltz et al 2012). To further investigate how telomerase activity levels are affected by DNA damage, 7-d-old wild-type seedlings were transferred to liquid culture containing 20 mM zeocin, and Q-TRAP was performed at different time intervals beginning 30 min after transfer to drug.…”

Section: Dna Damage-induced Repression Of Telomerase Activity Correlamentioning

confidence: 99%

“…S4B). In Arabidopsis, telomerase activity is wild type in G1 atr mutants but then declines dramatically in later generations (Boltz et al 2012). The mechanism underlying this repression is unknown but may reflect accumulating replication stress.…”

Section: Dna Damage-induced Repression Of Telomerase Activity Correlamentioning

confidence: 99%

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An alternative telomerase RNA in Arabidopsis modulates enzyme activity in response to DNA damage

et al. 2012

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Telomerase replenishes telomere tracts by reiteratively copying its RNA template, TER. Unlike other model organisms, Arabidopsis thaliana harbors two divergent TER genes. However, only TER1 is required for telomere maintenance. Here we examine the function of TER2. We show that TER2 is spliced and its 39 end is truncated in vivo to generate a third TER isoform, TER2 S . TERT preferentially associates with TER2 > TER1 > TER2 S . Moreover, TER2 and TER2 S assemble with Ku and POT1b (protection of telomeres), forming RNP (ribonucleoprotein) complexes distinct from TER1 RNP. Plants null for TER2 display increased telomerase enzyme activity, while TER2 overexpression inhibits telomere synthesis from TER1 and leads to telomere shortening. These findings argue that TER2 negatively regulates telomerase by sequestering TERT in a nonproductive RNP complex. Introduction of DNA double-strand breaks by zeocin leads to an immediate and specific spike in TER2 and a concomitant decrease in telomerase enzyme activity. This response is not triggered by replication stress or telomere dysfunction and is abrogated in ter2 mutants. We conclude that Arabidopsis telomerase is modulated by TER2, a novel DNA damageinduced noncoding RNA that works in concert with the canonical TER to promote genome integrity.

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Section: Ter2: a Novel Noncoding Rna Induced In Response To Dsbsmentioning

confidence: 49%

“…4F), although both mutations activate DDR ( Fig. 5A; Boltz et al 2012). In plants lacking TERT, all three TER isoforms were reduced, suggesting that TERT promotes their stability.…”

Section: Dna Damage-induced Repression Of Telomerase Activity Correlamentioning

confidence: 89%

Section: Dna Damage-induced Repression Of Telomerase Activity Correlamentioning

confidence: 99%

Section: Dna Damage-induced Repression Of Telomerase Activity Correlamentioning

confidence: 99%

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An alternative telomerase RNA in Arabidopsis modulates enzyme activity in response to DNA damage

et al. 2012

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“…We postulate that the effects of the mutation of rtel1-1 on DNA replication and HR might enhance the stringency of the activated cell cycle checkpoint pathways, with a synergistic growth inhibitory effect as a consequence. Simultaneously, as ATR contributes to telomere length maintenance (Amiard et al, 2011;Boltz et al, 2012), the rtel1-1 activated ATR pathway might account for the observed partial restoration of telomere length in rtel1-1 stn1-1 plants, compared with stn1-1.…”

Section: Discussionmentioning

confidence: 99%

Deficiency of the Arabidopsis Helicase RTEL1 Triggers a SOG1-Dependent Replication Checkpoint in Response to DNA Cross-Links

Cools

Kalhorzadeh

et al. 2015

The Plant Cell

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To maintain genome integrity, DNA replication is executed and regulated by a complex molecular network of numerous proteins, including helicases and cell cycle checkpoint regulators. Through a systematic screening for putative replication mutants, we identified an Arabidopsis thaliana homolog of human Regulator of Telomere Length 1 (RTEL1), which functions in DNA replication, DNA repair, and recombination. RTEL1 deficiency retards plant growth, a phenotype including a prolonged S-phase duration and decreased cell proliferation. Genetic analysis revealed that rtel1 mutant plants show activated cell cycle checkpoints, specific sensitivity to DNA cross-linking agents, and increased homologous recombination, but a lack of progressive shortening of telomeres, indicating that RTEL1 functions have only been partially conserved between mammals and plants. Surprisingly, RTEL1 deficiency induces tolerance to the deoxynucleotide-depleting drug hydroxyurea, which could be mimicked by DNA cross-linking agents. This resistance does not rely on the essential replication checkpoint regulator WEE1 but could be blocked by a mutation in the SOG1 transcription factor. Taken together, our data indicate that RTEL1 is required for DNA replication and that its deficiency activates a SOG1-dependent replication checkpoint.

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DDM1 guards against telomere truncation in Arabidopsis

Xie

Shippen

2018

Plant Cell Rep

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Epigenetic pathways, including DNA methylation, are crucial for telomere maintenance. Deficient in DNA Methylation 1 (DDM1) encodes a nucleosome remodeling protein, required to maintain DNA methylation in Arabidopsis thaliana. Plants lacking DDM1 can be self-propagated, but in the sixth generation (G6) hypomethylation leads to rampant transposon activation and infertility. Here we examine the role of DDM1 in telomere length homeostasis through a longitudinal study of successive generations of ddm1-2 mutants. We report that bulk telomere length remains within the wild-type range for the first five generations (G1–G5), and then precipitously drops in G6. While telomerase activity becomes more variable in later generation ddm1-2 mutants, there is no correlation between enzyme activity and telomere length. Plants lacking DDM1 also exhibit no dysregulation of several known telomere-associated transcripts, including TERRA. Instead, telomere shortening coincides with increased G-overhangs and extra-chromosomal circles, consistent with deletional recombination. Telomere shortening also correlates with transcriptional activation of retrotransposons, and a hypersensitive DNA damage response in root apical meristems. Since abiotic stresses, including DNA damage, stimulate homologous recombination, we hypothesize that telomere deletion in G6 ddm1-2 mutants is a by-product of elevated genome-wide recombination in response to trans-poson mobilization. Further, we speculate that telomere truncation may be beneficial in adverse environmental conditions by accelerating the elimination of stem cells with aberrant genomes.

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ATR cooperates with CTC1 and STN1 to maintain telomeres and genome integrity inArabidopsis

Cited by 22 publications

References 78 publications

An alternative telomerase RNA in Arabidopsis modulates enzyme activity in response to DNA damage

An alternative telomerase RNA in Arabidopsis modulates enzyme activity in response to DNA damage

Deficiency of the Arabidopsis Helicase RTEL1 Triggers a SOG1-Dependent Replication Checkpoint in Response to DNA Cross-Links

DDM1 guards against telomere truncation in Arabidopsis

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