Genome-wide excision repair in Arabidopsis is coupled to transcription and reflects circadian gene expression patterns

Oztas, Onur; Selby, Christopher P.; Sancar, Aziz; Adebali, Ogün

doi:10.1038/s41467-018-03922-5

Cited by 48 publications

(76 citation statements)

References 44 publications

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“…Next, repair across the sensitive and resistant cell lines were averaged. The average unit gene repair profiles in Figure 4C are similar to profiles seen in other human cell types, and in cells of other species, which show elevated TS repair which peaks near the TSS, and largely depressed non-transcribed strand (NTS) repair which peaks immediately upstream of the TSS and results from antisense transcription at the promoter (28)(29)(30)(31)(32). Figure 4C shows that overall, there is no difference in amount or pattern of genespecific repair between oxaliplatinsensitive and oxaliplatin-resistant cell lines.…”

Section: Oxaliplatin-sensitive and Oxaliplatinresistant Cell Lines Hasupporting

confidence: 67%

Genome-wide single-nucleotide resolution of oxaliplatin–DNA adduct repair in drug-sensitive and -resistant colorectal cancer cell lines

Vaughn

Selby

Yang

et al. 2020

Journal of Biological Chemistry

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Platinum-based chemotherapies, including oxaliplatin, are a mainstay in the management of solid tumors and induce cell death by forming intrastrand dinucleotide DNA adducts. Despite their common use, they are highly toxic, and approximately half of cancer patients have tumors that are either intrinsically resistant or develop resistance. Previous studies suggest that this resistance is mediated by variations in DNA repair levels or net drug influx. Here, we aimed to better define the roles of nucleotide excision repair and DNA damage in platinum chemotherapy resistance by profiling DNA damage and repair efficiency in seven oxaliplatin-sensitive and three oxaliplatin-resistant colorectal cancer cell lines. We assayed DNA repair indirectly as toxicity and directly measured bulky adduct formation and removal from the genome by slot blot and repair capacity in an excision assay, and used excision repair sequencing (XR-seq) to map repair events genome-wide at single-nucleotide resolution. Using this combinatorial approach and proxies for oxaliplatin–DNA damage, we observed no significant differences in repair efficiency that could explain the relative sensitivities and chemotherapy resistances of these cell lines. In contrast, the levels of oxaliplatin-induced DNA damage were significantly lower in the resistant cells, indicating that decreased damage formation, rather than increased damage repair, is a major determinant of oxaliplatin resistance in these cell lines. XR-seq–based analysis of gene expression revealed up-regulation of membrane transport pathways in the resistant cells, and these pathways may contribute to resistance. In conclusion, additional research is needed to characterize the factors mitigating cellular DNA damage formation by platinum compounds.

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Section: Oxaliplatin-sensitive and Oxaliplatinresistant Cell Lines Hasupporting

confidence: 67%

Genome-wide single-nucleotide resolution of oxaliplatin–DNA adduct repair in drug-sensitive and -resistant colorectal cancer cell lines

Vaughn

Selby

Yang

et al. 2020

Journal of Biological Chemistry

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“…Therefore, chromocenters reorganization upon UV-C exposure may reflects this slower repair kinetics and highlight that heterochromatic photodamage repair may require complex strategies as compared to euchromatic repair (Feng and Michaels, 2015). In agreement with this, excised photolesions are detected in the first 30 min following UV irradiation and overlap predominantly with RNA POL II targeted loci, a feature of the TCR pathway acting in euchromatin (Oztas et al, 2018).…”

Section: Photolesions Are Sources Of Dna Methylation Changes In Hetermentioning

confidence: 56%

Photodamage repair pathways contribute to the accurate maintenance of the DNA methylome landscape upon UV exposure

Graindorge

Cognat

Berens

et al. 2019

Preprint

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Plants are exposed to the damaging effect of sunlight that induces DNA photolesions. In order to maintain genome integrity, specific DNA repair pathways are mobilized. Upon removal of UV-induced DNA lesions, the accurate re-establishment of epigenome landscape is expected to be a prominent step of these DNA repair pathways. However, it remains poorly documented whether DNA methylation is accurately maintained at photodamaged sites and how photodamage repair pathways contribute to the maintenance of genome/methylome integrities.Using genome wide approaches, we report that UV-C irradiation leads to asymmetric DNA methylation changes. We identified that the specific DNA repair pathways involved in the repair of UV-induced DNA lesions, Direct Repair (DR) and Global Genome Repair (GGR), prevent the excessive alterations of DNA methylation landscape. Moreover, we identified that UV-C irradiation induced chromocenter reorganization and that photodamage repair factors control this dynamics. The methylome changes rely on misregulation of maintenance, de novo and active DNA demethylation pathways highlighting that molecular processes related to genome and methylome integrities are closely interconnected. Importantly, we identified that photolesions are sources of DNA methylation changes in both, constitutive and facultative heterochromatin. This study unveils that DNA repair factors, together with small RNA, act to accurately maintain both genome and methylome integrities at photodamaged silent genomic regions, strengthening the idea that plants have evolved sophisticated interplays between DNA methylation dynamics and DNA repair. Availability of data and materialsWGBS, DNA-seq and small RNA-seq raw data generated in this work are publicly accessible through the GEO registration number : GSE132750. Authors' contributionsSG and VC performed bioinformatics. PJtoB performed cytogenetics, developed the automated image analysis program with JMu and analyzed the data. SG, VC, PJtoB and JMu wrote the methods section. JM designed experiments, prepared the biological samples, analyzed the data and wrote the manuscript. All authors read and approved the final manuscript.

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“…The plant circadian clock entrained by environmental stimuli coordinates biological processes on a daily basis and enables proper growth and development (1)(2)(3). The circadian oscillator consists of multiple interlocked transcriptional feedback loops, formed by the sequential induction of core-clock genes acting as reciprocal transcriptional repressors throughout the day (4).…”

Section: Introductionmentioning

confidence: 99%

The circadian clock shapes the Arabidopsis transcriptome by regulating alternative splicing and alternative polyadenylation

Yang

Sancar

et al. 2020

Journal of Biological Chemistry

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The circadian clock in plants temporally coordinates biological processes throughout the day, synchronizing gene expression with diurnal environmental changes. Circadian oscillator proteins are known to regulate the expression of clock-controlled plant genes by controlling their transcription. Here, using a high-throughput RNA-Seq approach, we examined genome-wide circadian and diurnal control of the Arabidopsis transcriptome, finding that the oscillation patterns of different transcripts of multitranscript genes can exhibit substantial differences and demonstrating that the circadian clock affects posttranscriptional regulation. In parallel, we found that two major posttranscriptional mechanisms, alternative splicing (AS; especially intron retention) and alternative polyadenylation (APA), display circadian rhythmicity resulting from oscillation in the genes involved in AS and APA. Moreover, AS-related genes exhibited rhythmic AS and APA regulation, adding another layer of complexity to circadian regulation of gene expression. We conclude that the Arabidopsis circadian clock not only controls transcription of genes but also affects their posttranscriptional regulation by influencing alternative splicing and alternative polyadenylation.

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Genome-wide excision repair in Arabidopsis is coupled to transcription and reflects circadian gene expression patterns

Cited by 48 publications

References 44 publications

Genome-wide single-nucleotide resolution of oxaliplatin–DNA adduct repair in drug-sensitive and -resistant colorectal cancer cell lines

Genome-wide single-nucleotide resolution of oxaliplatin–DNA adduct repair in drug-sensitive and -resistant colorectal cancer cell lines

Photodamage repair pathways contribute to the accurate maintenance of the DNA methylome landscape upon UV exposure

The circadian clock shapes the Arabidopsis transcriptome by regulating alternative splicing and alternative polyadenylation

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