A multispecies toolkit of TOP2 hypercleavage mutants for studying topoisomerase II-mediated DNA damage.

doi:10.1073/pnas.2616452123

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Article

A multispecies toolkit of TOP2 hypercleavage mutants for studying topoisomerase II-mediated DNA damage.

Proceedings of the National Academy of Sciences of the United States of America - 8 Sept 2026

Ontoso David, Mehta Monika, Shabro Aidin, Dittmar John, Reid Robert J D, Rothstein Rodney, Nitiss John L, Keeney Scott

Abstract excerpt

DNA topoisomerase II (TOP2) generates transient DNA double-strand breaks that are trapped as TOP2-DNA covalent complexes (TOP2cc) by antibiotic and chemotherapy drugs. Here, we characterize tools for study of cellular responses to TOP2cc, exploiting a Saccharomyces cerevisiae TOP2 mutant (TOP2-F1025Y,R1128G) that generates spontaneous and inhibitor-induced covalent complexes at elevated frequencies. This Top2-hc...

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Topics

DNA Topoisomerases, Type II
Saccharomyces cerevisiae
Animals
Saccharomyces cerevisiae Proteins
Humans

Methodology Data sources Editorial policy Privacy Delete account & data About Contact Helena Bioinformatics

Poly-ADP-Ribose Binding Proteins

Mice

DNA Damage

Topoisomerase II Inhibitors

Mutation

DNA Breaks, Double-Stranded

DNA Repair

Antigens, Neoplasm

Source

Open in PubMed Open full text

Identifiers

PMID: 42679034
DOI: 10.1073/pnas.2616452123
PMCID: PMC13552660

Genes

TOP2A
TOP2B

Provenance

PubMed metadata and Literature Corpus relationships. Corpus snapshot updated 23 Oct 2026.

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