Date of Completion

Spring 5-18-2026

Thesis Advisor(s)

Raman Bahal

Honors Major

Molecular and Cell Biology

Disciplines

Nucleic Acids, Nucleotides, and Nucleosides | Pharmaceutical Preparations

Abstract

DNA strand breaks are among the most critical forms of genomic damage, arising from endogenous metabolic activity, environmental stress, radiation, and diverse chemical agents. Single-strand breaks and double-strand breaks contribute to genome instability, mutagenesis, carcinogenesis, and neurodegenerative disorders. Cells rely on DNA repair pathways to detect these breaks and initiate repair. In this review, we conducted a comprehensive literature review to systematically compile and examine the mechanisms underlying small-molecule-induced DNA strand breaks. This review highlights the underlying mechanisms by which these molecules interact with DNA and trigger damage. We further discussed the current methods used for detection and quantification of DNA strand breaks, emphasizing their application in molecular biology and translational research. In addition, we hypothesized a future strategy for sequence-specific genome targeting by employing DNA-cleaving small molecules in combination with peptide nucleic acids (PNA). Such conjugates may provide an alternative to conventional nuclease-based technologies by potentially improving targeting precision while minimizing off-target effects. Overall, this review presents DNA damage not only as a source of cellular toxicity but also as a valuable tool for precision medicine, gene repair, and next-generation therapeutic development.

Keywords: Small molecules, DNA strand breaks, single-strand break, double-strand break

Accessibility Requirements

1

Download

Share

COinS