Single-nucleotide resolution dynamic repair maps of UV damage in
            <i>Saccharomyces cerevisiae</i>
            genome

Li, Wentao; Adebali, Ogün; Yang, Yanyan; Selby, Christopher P.; Sancar, Aziz

doi:10.1073/pnas.1801687115

Cited by 43 publications

(103 citation statements)

References 49 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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“…Although TCR analysis has been performed in yeast, Arabidopsis, humans, and a few other eukaryotic species (26)(27)(28)(29), it has not been extensively performed in prokaryotes with the exception of E. coli (17,24,25), even though the TCR factor Mfd has been found in all nonendosymbiotic bacteria including mycobacteria (9). Here we use our XR-seq data to analyze TCR in M. smegmatis as a sentinel for all other Mfd-containing bacteria.…”

Section: Transcription-coupled Repair In Mycobacteriamentioning

confidence: 99%

Mycobacteria excise DNA damage in 12- or 13-nucleotide-long oligomers by prokaryotic-type dual incisions and performs transcription-coupled repair

Selby

Lindsey-Boltz

Yang

et al. 2020

Journal of Biological Chemistry

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In nucleotide excision repair, bulky DNA lesions such as UV-induced cyclobutane pyrimidine dimers (CPDs) are removed from the genome by concerted dual incisions bracketing the lesion, followed by gap filling and ligation. So far, two dual incision patterns have been discovered: prokaryotic type which removes the damage in 11-13 nucleotide-long oligomers and eukaryotic type which removes the damage in 24-32 nucleotide-long oligomers. However, a recent study reported that the UvrC protein of Mycobacterium tuberculosis removes damage in a manner analogous to yeast and humans in a 25-mer oligonucleotide arising from incisions at 15 nucleotides from the 3’ end and 9 nucleotides from the 5’ end flanking the damage. To test this model, we used the in vivo excision assay and the XR-seq genome-wide repair mapping method developed in our lab to determine the repair pattern and genome-wide repair map of M. smegmatis. We find that M. smegmatis, which possesses homologues of the E. coliuvrA, B, and C genes, removes CPDs from the genome in a manner identical to the prokaryotic pattern by incising 7 nucleotides 5’ and 3 or 4 nucleotides 3’ to the photoproduct, and performs transcription-coupled repair in a manner similar to E. coli.

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“…Nucleotide excision repair in human, S. cerevisiae and E. coli was shown to yield primary excised oligomers predominantly in lengths of 27, 24 and 13 nucleotides, respectively (Hu et al 2013;Huang et al 1992;Li et al 2018;Sancar and Rupp 1983;Adebali et al 2017 a).…”

Section: Excised Oligomer Characteristicsmentioning

confidence: 99%

Comparative analyses of two primate species diverged by more than 60 million years show different rates but similar distribution of genome-wide UV repair events

Akköse

Kaya

Lindsey-Boltz

et al. 2020

Preprint

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Nucleotide excision repair is the primary DNA repair mechanism that removes bulky DNA adducts such as UV-induced pyrimidine dimers. Correspondingly, genome-wide mapping of nucleotide excision repair with eXcision Repair sequencing (XR-seq), provides comprehensive pro ling of DNA damage repair. A number of XR-seq experiments at a variety of conditions for di erent damage types revealed heterogenous repair in the human genome. Although human repair pro les were extensively studied, how repair maps vary between primates is yet to be investigated. Here, we characterized the genome-wide UV-induced damage repair in gray mouse lemur,Microcebus murinus, in comparison to human. Mouse lemurs are strictly nocturnal, are the world's smallest living primates, and last shared a common ancestor with humans at least 60 million years ago. We derived broblast cell lines from mouse lemur, exposed them to UV irradiation. The following repair events were captured genome-wide through the XR-seq protocol. Mouse lemur repair pro les were analyzed in comparison to the equivalent human broblast datasets. We found that overall UV sensitivity, repair e ciency, and transcription-coupled repair levels di er between the two primates. Despite this, comparative analysis of human and mouse lemur broblasts revealed that genome-wide repair pro les of the homologous regions are highly correlated. This correlation is stronger for the highly expressed genes. With the inclusion of an additional XR-seq sample derived from another human cell line in the analysis, we found that broblasts of the two primates repair UV-induced DNA lesions in a more similar pattern than two distinct human cell lines do. Our results suggest that mouse lemurs and humans, and possibly primates in general, share a homologous repair mechanism as well as genomic variance distribution, albeit with their variable repair e ciency. This result also emphasizes the deep homologies of individual tissue types across the eukaryotic phylogeny.

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Single-nucleotide resolution dynamic repair maps of UV damage in Saccharomyces cerevisiae genome

Cited by 43 publications

References 49 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

Mycobacteria excise DNA damage in 12- or 13-nucleotide-long oligomers by prokaryotic-type dual incisions and performs transcription-coupled repair

Comparative analyses of two primate species diverged by more than 60 million years show different rates but similar distribution of genome-wide UV repair events

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