Cancer therapeutics and mechanisms

Genome-wide mapping of endogenous topoisomerase cleavage complexes reveals TOP1 at the interface of DNA topological regulation and genome instability

This study introduces pDAIP-seq, a method to map endogenous topoisomerase cleavage complexes, revealing their genomic distribution and role in DNA breaks and genome instability.

Negative supercoiling facilitates human TOP3α-mediated decatenation of DNA braids via catenation junction melting

The paper shows that negative supercoiling enables TOP3α to resolve DNA braids by melting crossings into single-stranded DNA, facilitated by TRR and RPA.

Type II topoisomerase substrate geometry revealed through combined experiment and computation.

This study determines the 3D geometry of DNA crossings preferred for strand passage by topo II enzymes using single-molecule experiments and simulations.

Systematic Generation of Mutations at Topoisomerase II Cleavage Sites Enables Cancer Adaptation to Doxorubicin Therapy

The paper shows that cancer cells develop resistance to doxorubicin by accumulating mutations at Top2 cleavage sites, which prevent DNA damage and promote adaptation.

Cryo-EM structural analysis of human TOP1 trapping by eight clinical anticancer drugs

The paper presents cryo-EM structures of human TOP1cc bound to eight anticancer drugs, revealing structural differences and insights for drug design.

ZATT/ZNF451 promotes release of stalled TOP2 cleavage complexes

This study identifies ZATT/ZNF451 as a key factor in resolving stalled TOP2 cleavage complexes without relying on TDP2, proteolysis, or DSB repair pathways.

Topoisomerase IIIα resolves inter- and intra-molecular intertwines during DNA replication

This study shows that TOP3 resolves both inter- and intra-molecular DNA intertwines during replication, promoting fork progression and daughter strand unlinking, especially when TOP2 is compromised.

Assessing Corynebacterium glutamicum as a surrogate of Mycobacterium tuberculosis for DNA gyrase inhibitor design.

This paper validates Corynebacterium glutamicum as a non-pathogenic surrogate for Mycobacterium tuberculosis to study DNA gyrase and discover new inhibitors.

Investigation of potential hinge region for Mycobacterium tuberculosis topoisomerase I conformational change during catalysis

The paper identifies a potential hinge region in MtbTOP1 critical for conformational changes during DNA relaxation, showing that mutations disrupt enzyme activity.

Computational insights into the interaction between Topoisomerase I and Rpc82 subunit of RNA Polymerase III in Saccharomyces cereviseae

The paper presents a computational model of yeast Top1 and identifies key residues mediating its interaction with Rpc82, a subunit of RNA polymerase III.

Binding Kinetics Oppositely Regulates type II Topoisomerase Relaxation and Decatenation Activities

This study shows that topo II binding kinetics oppositely regulate decatenation and relaxation activities through a trade-off between search efficiency and processivity.

Identification of novel human topoisomerase III beta inhibitors

The paper identifies potential inhibitors of TOP3B using molecular dynamics and docking, showing that bemcentinib and its analogs inhibit TOP3B relaxation activity.

Topoisomerase IIIb protects from tumorigenesis and immune dysregulation

This study shows that Top3b loss accelerates lymphoma development and causes immune dysregulation in mice through R-loop accumulation and immune signaling activation.

Targeting SUV4-20H epigenetic enzymes as therapeutic strategy for enhancing topoisomerase II poisoning in prostate cancer

This study shows that inhibiting SUV4-20H enzymes enhances the effectiveness of TOP2 poisons in prostate cancer by increasing DNA damage and impairing repair mechanisms.

DNA topoisomerase I acts as supercoiling sensor for transcription elongation in E. coli

The paper investigates how DNA topoisomerase I senses and responds to supercoiling during transcription elongation in E. coli.

A Yeast-Based Screening System for Differential Identification of Poison Inhibitors and Catalytic Inhibitors of Human Topoisomerase I

This paper develops a yeast-based screening system to identify human TOP1 poison inhibitors and catalytic inhibitors, distinguishing their mechanisms and assessing cytotoxicity.

Bacterial type 1A topoisomerases maintain the stability of the genome by preventing and dealing with R-loop-and nucleotide excision repair-dependent topological stress.

The paper shows that type 1A topoisomerases prevent and resolve topological stress from R-loops and nucleotide excision repair in E. coli by providing relaxase and decatenase activities.

Recurrent mutations in topoisomerase 2a cause a novel mutator phenotype in human cancers

The paper identifies a novel mutator phenotype, ID_TOP2A, caused by the TOP2A p.K743N mutation, characterized by specific small indels and associated with tumorigenesis.

Topoisomerase IIβ targets DNA crossovers formed between distant homologous sites to modulate chromatin structure and gene expression

The paper identifies two modes of topoisomerase IIβ action, showing it resolves distant DNA crossovers to regulate chromatin structure and gene expression during neuronal differentiation.