Genome-wide alterations of uracil distribution patterns in human DNA upon chemotherapeutic treatments.
U-DNA-Seq
anti-cancer drug treatment
chromosomes
gene expression
genome-wide mapping
human
super-resolution microscopy
uracil-DNA
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
21 09 2020
21 09 2020
Historique:
received:
29
06
2020
accepted:
23
08
2020
entrez:
21
9
2020
pubmed:
22
9
2020
medline:
2
3
2021
Statut:
epublish
Résumé
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
Identifiants
pubmed: 32956035
doi: 10.7554/eLife.60498
pii: 60498
pmc: PMC7505663
doi:
pii:
Substances chimiques
Antineoplastic Agents
0
Uracil
56HH86ZVCT
DNA
9007-49-2
Banques de données
GEO
['GSE126822', 'GSE153407', 'GSE99011']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : National Research, Development and Innovation Office of Hungary
ID : KH-129581
Pays : International
Organisme : National Research, Development and Innovation Office of Hungary
ID : VEKOP-2.3.2-16-2017-00013
Pays : International
Organisme : National Research, Development and Innovation Office of Hungary
ID : NKP-2018-1.2.1-NKP-2018-00005
Pays : International
Organisme : NIGMS NIH HHS
ID : R35 GM136250
Pays : United States
Organisme : National Research, Development and Innovation Office of Hungary
ID : 2017-1.3.1-VKE-2017-00013
Pays : International
Organisme : National Research, Development and Innovation Office of Hungary
ID : 2018-1.3.1-VKE-2018-00032
Pays : International
Organisme : National Research, Development and Innovation Office of Hungary
ID : NVKP_16-1-2016-0020
Pays : International
Organisme : National Research, Development and Innovation Office of Hungary
ID : K119493
Pays : International
Organisme : National Research, Development and Innovation Office of Hungary
ID : 2017-1.3.1-VKE-2017-00002
Pays : International
Organisme : National Research, Development and Innovation Office of Hungary
ID : NVKP_16-1-2016-0037
Pays : International
Organisme : NCI NIH HHS
ID : R01 CA076584
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM134947
Pays : United States
Organisme : Ministry of Human Capacities
ID : BME FIKP-BIO
Pays : International
Organisme : NIGMS NIH HHS
ID : R01 GM108119
Pays : United States
Organisme : Cancer Research UK
ID : C37/A18784
Pays : United Kingdom
Informations de copyright
© 2020, Pálinkás et al.
Déclaration de conflit d'intérêts
HP, AB, GR, LP, GP, GT, EH, ÁP, CG, SA, MM, ER, MP, DS, BG, BV No competing interests declared
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