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Genome-wide alterations of uracil distribution patterns in human DNA upon chemotherapeutic treatments.

ABSTRACT: Numerous anti-cancer drugs perturb thymidylate biosynthesis and lead to genomic uracil incorporation contributing to their antiproliferative effect. Still, it is not yet characterized if uracil incorporations have any positional preference. Here, we aimed to uncover genome-wide alterations in uracil pattern upon drug treatments in human cancer cell line models derived from HCT116. We developed a straightforward U-DNA sequencing method (U-DNA-Seq) that was combined with in situ super-resolution imaging. Using a novel robust analysis pipeline, we found broad regions with elevated probability of uracil occurrence both in treated and non-treated cells. Correlation with chromatin markers and other genomic features shows that non-treated cells possess uracil in the late replicating constitutive heterochromatic regions, while drug treatment induced a shift of incorporated uracil towards segments that are normally more active/functional. Data were corroborated by colocalization studies via dSTORM microscopy. This approach can be applied to study the dynamic spatio-temporal nature of genomic uracil.

SUBMITTER: Palinkas HL

PROVIDER: S-EPMC7505663 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Genome-wide alterations of uracil distribution patterns in human DNA upon chemotherapeutic treatments.

Pálinkás Hajnalka L HL Békési Angéla A Róna Gergely G Pongor Lőrinc L Papp Gábor G Tihanyi Gergely G Holub Eszter E Póti Ádám Á Gemma Carolina C Ali Simak S Morten Michael J MJ Rothenberg Eli E Pagano Michele M Szűts Dávid D Győrffy Balázs B Vértessy Beáta G BG

eLife 20200921

Numerous anti-cancer drugs perturb thymidylate biosynthesis and lead to genomic uracil incorporation contributing to their antiproliferative effect. Still, it is not yet characterized if uracil incorporations have any positional preference. Here, we aimed to uncover genome-wide alterations in uracil pattern upon drug treatments in human cancer cell line models derived from HCT116. We developed a straightforward U-DNA sequencing method (U-DNA-Seq) that was combined with in situ super-resolution i ...[more]

PMID: 32956035

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Genome-wide alterations of uracil distribution patterns in human DNA upon chemotherapeutic treatments.

Publications

Genome-wide alterations of uracil distribution patterns in human DNA upon chemotherapeutic treatments.

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