Work

Effects of mirror-image nucleosides on DNA replication and transcription in human cells

Year: 2024

Type: article

Abstract: Mirror-image nucleosides, as potential antiviral drugs, can inhibit virus DNA polymerase to prevent virus replication. Conversely, they may be inserted into the DNA strands during DNA replication or transcription processes, leading to mutations that affect genome stability. Accumulation of significant mutation damage in cells may result in cell aging, apoptosis, and even uncontrolled cell division. We have previously explored the efficiency and fidelity of replication across mirror-image nucleosides within Escherichia coli, and this study focuses on human cells. We constructed several plasmid substrates, each carrying a specific mirror-image nucleoside, to investigate their impact on intracellular DNA replication and transcription processes. The results showed that in HepG2 cells, L-adenosine was the most potent substrate in inhibiting cell replication and transcription. L-cytidine exhibited the highest bypass efficiency in both template strands or nontemplate strands and had the most diverse mutation types. We also observed that L-cytidine induced immunoregulation of the JAK-STAT signaling pathway. Therefore, our results provide a theoretical basis for the disruptions caused by mirror-image nucleosides in replication and transcription and give us some understanding that mirror-image nucleoside drugs can cause cytotoxicity.

Source: Journal of Biological Chemistry

DOI: 10.1016/j.jbc.2024.108139

Authors: Zhaoyang Jin, Yifei Wang, Shuaishuai Cui, Yujian He, Li Wu

Institutions: University of Chinese Academy of Sciences, Hebei Normal University, Peking University, State Key Laboratory of Natural and Biomimetic Drugs

Language: English

Topic: DNA and Nucleic Acid Chemistry

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,800