Ad-Seq, a genome-wide DNA-adduct profiling assay

Harismendy, O.; Howell, S.

doi:10.1101/364794

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bioRxiv · 10.1101/364794

Ad-Seq, a genome-wide DNA-adduct profiling assay

Harismendy, O.·Howell, S.

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Abstract

SummaryCarcinogens form adducts with the DNA which, when not properly repaired, can lead to mutations and drive oncogenesis. The identity, sequence specificity and mutagenicity of most DNA-adducts is however poorly understood and current molecular assays are limited in their scope and scalability. We present a novel genome-wide DNA adduct sequencing (Ad-Seq) assay to map the location of DNA-adducts at single-nucleotide resolution. Ad-Seq enriches for DNA fragments containing nuclease digestion resistant DNA-adducts. The genomic location of the resulting reads is aggregated in a quantitative profile showing the DNA-adduct sequence context. Ad-Seq is quantitative and confirms known specificity of damages from Ultra-Violet light (di-pyrimidine) and cisplatin (AG and GG di-purines). Furthermore, in cells, Ad-Seq profile can be compared to chromatin segments to show that cisplatin associated adducts are depleted in open and active chromatin regions. The Ad-Seq assay can therefore generate a broad DNA signature of DNA damage and, by comparing to mutagen exposure or downstream mutational profile and signatures, be used to improve our understanding of cancer molecular etiology.

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Harismendy, O., Howell, S.. 2018-07-08. Ad-Seq, a genome-wide DNA-adduct profiling assay. https://doi.org/10.1101/364794

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