Imperial College London
Alternate

ProfessorCharlesCoombes

Faculty of Medicine, Department of Surgery & Cancer

Emeritus Professor of Medical Oncology
 
 
 
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Contact

 

+44 (0)20 7594 2135c.coombes

 
 
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Assistant

 

Mrs Suzy Ford +44 (0)20 7594 2135

 
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Location

 

145ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Palinkas:2020:10.7554/eLife.60498,
author = {Palinkas, HL and Bekesi, A and Rona, G and Pongor, L and Papp, G and Tihanyi, G and Holub, E and Poti, A and Gemma, C and Ali, S and Morten, MJ and Rothenberg, E and Pagano, M and Szuts, D and Gyorffy, B and Vertessy, BG},
doi = {10.7554/eLife.60498},
journal = {eLife},
pages = {1--37},
title = {Genome-wide alterations of uracil distribution patterns in human DNA upon chemotherapeutic treatments},
url = {http://dx.doi.org/10.7554/eLife.60498},
volume = {9},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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.
AU  - Palinkas,HL
AU  - Bekesi,A
AU  - Rona,G
AU  - Pongor,L
AU  - Papp,G
AU  - Tihanyi,G
AU  - Holub,E
AU  - Poti,A
AU  - Gemma,C
AU  - Ali,S
AU  - Morten,MJ
AU  - Rothenberg,E
AU  - Pagano,M
AU  - Szuts,D
AU  - Gyorffy,B
AU  - Vertessy,BG
DO  - 10.7554/eLife.60498
EP  - 37
PY  - 2020///
SN  - 2050-084X
SP  - 1
TI  - Genome-wide alterations of uracil distribution patterns in human DNA upon chemotherapeutic treatments
T2  - eLife
UR  - http://dx.doi.org/10.7554/eLife.60498
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000574934800001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://elifesciences.org/articles/60498
UR  - http://hdl.handle.net/10044/1/84060
VL  - 9
ER  -
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