Characteristic effect of hydroxyurea on the higher-order structure of DNA and gene expression

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

Abstract

Hydroxyurea (HU; hydroxycarbamide) is a chemotherapy medication used to treat various types of cancer and other diseases such as sickle cell anemia. HU inhibits DNA synthesis by targeting ribonucleotide reductase (RNR). Recent studies have suggested that HU also causes oxidative stress in living systems. In the present study, we investigated if HU could directly affect the activity and/or conformation of DNA. We measured in vitro gene expression in the presence of HU by adapting a cell-free luciferase assay. HU exhibited a bimodal effect on gene expression, where promotion or inhibition were observed at lower or higher concentrations (mM range), respectively. Using atomic force microscopy (AFM), the higher-order structure of DNA was revealed to be partially-thick with kinked-branching structures after HU was added. An elongated coil conformation was observed by AFM in the absence of HU. Single DNA molecules in bulk aqueous solution under fluctuating Brownian motion were imaged by fluorescence microscopy (FM). Both spring and damping constants, mechanical properties of DNA, increased when HU was added. These experimental investigations indicate that HU directly interacts with DNA and provide new insights into how HU acts as a chemotherapeutic agent and targets other diseases.

Details

OriginalspracheEnglisch
Aufsatznummer13826
Seitenumfang9
FachzeitschriftScientific reports
Jahrgang14 (2024)
Ausgabenummer1
PublikationsstatusVeröffentlicht - 15 Juni 2024
Peer-Review-StatusJa

Externe IDs

PubMed 38879539
ORCID /0000-0001-8761-1776/work/162345648

Schlagworte

Ziele für nachhaltige Entwicklung

ASJC Scopus Sachgebiete

Schlagwörter

  • Gene Expression/drug effects, Hydroxyurea/pharmacology, DNA/metabolism, Humans, Microscopy, Atomic Force, Nucleic Acid Conformation/drug effects