Genome-wide alterations of uracil distribution patterns in human DNA upon chemotherapeutic treatments
Abstrak
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.
Penulis (16)
Hajnalka L Pálinkás
Angéla Békési
Gergely Róna
Lőrinc Pongor
Gábor Papp
Gergely Tihanyi
Eszter Holub
Ádám Póti
Carolina Gemma
Simak Ali
Michael J Morten
Eli Rothenberg
Michele Pagano
Dávid Szűts
Balázs Győrffy
Beáta G Vértessy
Akses Cepat
- Tahun Terbit
- 2020
- Bahasa
- en
- Total Sitasi
- 20×
- Sumber Database
- CrossRef
- DOI
- 10.7554/elife.60498
- Akses
- Open Access ✓