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G-quadruplex on Chromosomal DNA Negatively Regulates Topoisomerase 1 Activity

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE239694 | GEO | 2024/01/01

REPOSITORIES: GEO

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G-quadruplex on Chromosomal DNA Negatively Regulates Topoisomerase 1 Activity [CUT&Tag]

Project description:Human DNA topoisomerase 1 (Top1) is a crucial enzyme responsible for alleviating torsional stress on DNA during transcription and replication, thereby maintaining genome stability. Previous researches had found that non-working Top1 interacted extensively with chromosomal DNA in human cells. However, the reason for its retention on chromosomal DNA remained unclear. In this study, we discovered a close association between Top1 and chromosomal DNA, specifically linked to the presence of G-quadruplex (G4) structures. G4 structures, formed during transcription, trap Top1 and hinder its ability to relax neighboring DNAs. Disruption of the Top1-G4 interaction using G4 ligand relieved the inhibitory effect of G4 on Top1 activity, resulting in a further reduction of R-loop levels in cells. Additionally, the activation of Top1 through the use of a G4 ligand enhanced the toxicity of Top1 inhibitors towards cancer cells. Our study uncovers a negative regulation mechanism of human Top1 and highlights a novel pathway for activating Top1.

2024-01-01 | GSE239690 | GEO

G-quadruplex on Chromosomal DNA Negatively Regulates Topoisomerase 1 Activity [ChIP-seq]

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