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FUS drives the formation of biomolecular condensates in cells. Here, the authors reveal the dynamics and biophysical properties of FUS nanoclusters, an intermediate state in the phase separation pathway of FUS.

Here the authors by applying a single-molecule detection platform enabling FRET measurement on a long plasmid DNA construct, provide detailed insights on how negatively supercoiled DNA impacts co-transcriptional R-loop and G4 formation.

How chemotherapeutic nucleoside 6-thio-2’-deoxyguanosine (6-thiodG) targets telomerase to inhibit telomere maintenance in cancer cells and tumors was unclear. Here, the authors show that telomere length and telomerase status determine 6-thio-dG sensitivity and uncover the molecular mechanism by which 6-thio-dG selectively inhibits telomerase synthesis of telomeric DNA.

In eukaryotes, G-quadruplex in mRNA (RG4) 5′ UTR inhibit translation initiation. Here the authors employ single molecule assay to show that RG4 in E. coli reporter increases translation efficiency by preventing ribosome dislodging.

TDP-43 controls an exon splicing event in UNC13A that results in the inclusion of a cryptic exon associated with frontotemporal dementia and amyotrophic lateral sclerosis.

The antiviral dsRNA sensor PKR is regulated by PACT. This paper shows how PACT prevents aberrant PKR activation by endogenous dsRNAs like Alu. PACT disrupts PKR’s dsRNA scanning without blocking its binding, resetting its activation threshold to tolerate cellular dsRNA and preserve homeostasis.

G-quadruplex (G4) forming sequences are highly enriched in the human genome and function as important regulators of diverse range of biological processes. Here the authors show that while G4 structures on template strand block transcription, folding on the non-template strand enhances transcription by means of successive R-loop formation.

The realization that the cell is abundantly compartmentalized into biomolecular condensates has opened new opportunities for understanding the physics and chemistry underlying many cellular processes¹, fundamentally changing the study of biology². The term biomolecular condensate refers to non-stoichiometric assemblies that are composed of multiple types of macromolecules in cells, occur through phase transitions, and can be investigated by using concepts from soft matter physics³. As such, they are intimately related to aqueous two-phase systems⁴ and water-in-water emulsions⁵. Condensates possess tunable emergent properties such as interfaces, interfacial tension, viscoelasticity, network structure, dielectric permittivity, and sometimes interphase pH gradients and electric potentials^6–14. They can form spontaneously in response to specific cellular conditions or to active processes, and cells appear to have mechanisms to control their size and location^15–17. Importantly, in contrast to membrane-enclosed organelles such as mitochondria or peroxisomes, condensates do not require the presence of a surrounding membrane.

PCR is an essential method for the amplification and manipulation of nucleic acids, but the requirement for a thermocycler limits access. Here, authors engineer a helicase to replace the heating step of PCR with enzymatic unwinding, allowing the isothermal amplification of fragments up to 6 kb.

Srs2 is a DNA helicase and single-stranded DNA translocase that prevents homologous recombination by dismantling Rad51 filaments. Qiu et al.use single-molecule techniques to describe Rad51 filament formation and show that Srs2 displays repetitive activity on single-stranded DNA, which prevents re-formation of Rad51 filaments after dismantling.

DHX36 is a G-quadruplex (G4) resolving helicase that targets both DNA-G4 and RNA-G4. Here the authors use single molecule FRET measurements and show that DHX36 resolves RNA-G4 structures by a mechanism involving an ATP-dependent, highly repetitive and stepwise refolding of RNA-G4 that differs from its DNA-G4 structures resolving mechanism.

How G-quadruplexes (G4s) are resolved by helicases is still a matter of investigation. Here the authors provide mechanistic insight into G4s unwinding by presenting a crystal structure of resolved G4 DNA and the G4 binding domain of RecQ helicase from the bacterium Cronobacter sakazakii.

Opposing effects of 8-oxodGTP on telomerase activity – promoting elongation by destabilizing G4 structures or inhibiting elongation by acting as a chain terminator – explain the differential sensitivity of cells with short telomeres to oxidative stress.

A mechanism for the unfolding of guanine-rich DNA ‘quadruplexes’ by helicases is suggested, based on the structure of a DNA-bound helicase.