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1. Structure and luminescence of DNA-templated silver clusters

   https://doi.org/10.1039/D0NA01005G  

   Gonzàlez-Rosell, Anna ; Cerretani, Cecilia ; Mastracco, Peter ; Vosch, Tom ; Copp, Stacy M. ( March 2021 , Nanoscale Advances)

   null (Ed.)

   DNA serves as a versatile template for few-atom silver clusters and their organized self-assembly. These clusters possess unique structural and photophysical properties that are programmed into the DNA template sequence, resulting in a rich palette of fluorophores which hold promise as chemical and biomolecular sensors, biolabels, and nanophotonic elements. Here, we review recent advances in the fundamental understanding of DNA-templated silver clusters (Ag N -DNAs), including the role played by the silver-mediated DNA complexes which are synthetic precursors to Ag N -DNAs, structure–property relations of Ag N -DNAs, and the excited state dynamics leading to fluorescence in these clusters. We also summarize the current understanding of how DNA sequence selects the properties of Ag N -DNAs and how sequence can be harnessed for informed design and for ordered multi-cluster assembly. To catalyze future research, we end with a discussion of several opportunities and challenges, both fundamental and applied, for the Ag N -DNA research community. A comprehensive fundamental understanding of this class of metal cluster fluorophores can provide the basis for rational design and for advancement of their applications in fluorescence-based sensing, biosciences, nanophotonics, and catalysis. 

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2. A single nucleobase tunes nonradiative decay in a DNA-bound silver cluster

   https://doi.org/10.1063/5.0056836  

   Zhang, Yuyuan ; He, Chen ; de La Harpe, Kimberly ; Goodwin, Peter M. ; Petty, Jeffrey T. ; Kohler, Bern ( September 2021 , The Journal of Chemical Physics)

   DNA strands are polymeric ligands that both protect and tune molecular-sized silver cluster chromophores. We studied single-stranded DNA C4AC4TC3XT4 with X = guanosine and inosine that form a green fluorescent Ag106+ cluster, but these two hosts are distinguished by their binding sites and the brightness of their Ag106+ adducts. The nucleobase subunits in these oligomers collectively coordinate this cluster, and fs time-resolved infrared spectra previously identified one point of contact between the C2–NH2 of the X = guanosine, an interaction that is precluded for inosine. Furthermore, this single nucleobase controls the cluster fluorescence as the X = guanosine complex is ∼2.5× dimmer. We discuss the electronic relaxation in these two complexes using transient absorption spectroscopy in the time window 200 fs–400 µs. Three prominent features emerged: a ground state bleach, an excited state absorption, and a stimulated emission. Stimulated emission at the earliest delay time (200 fs) suggests that the emissive state is populated promptly following photoexcitation. Concurrently, the excited state decays and the ground state recovers, and these changes are ∼2× faster for the X = guanosine compared to the X = inosine cluster, paralleling their brightness difference. In contrast to similar radiative decay rates, the nonradiative decay rate is 7× higher with the X = guanosine vs inosine strand. A minor decay channel via a dark state is discussed. The possible correlation between the nonradiative decay and selective coordination with the X = guanosine/inosine suggests that specific nucleobase subunits within a DNA strand can modulate cluster–ligand interactions and, in turn, cluster brightness. 

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3. Structural evolution of a DNA repair self-resistance mechanism targeting genotoxic secondary metabolites

   https://doi.org/10.1038/s41467-021-27284-7  

   Mullins, Elwood_A ; Dorival, Jonathan ; Tang, Gong-Li ; Boger, Dale_L ; Eichman, Brandt_F ( November 2021 , Nature Communications)

   Microbes produce a broad spectrum of antibiotic natural products, including many DNA-damaging genotoxins. Among the most potent of these are DNA alkylating agents in the spirocyclopropylcyclohexadienone (SCPCHD) family, which includes the duocarmycins, CC-1065, gilvusmycin, and yatakemycin. The yatakemycin biosynthesis cluster inStreptomycessp. TP-A0356 contains an AlkD-related DNA glycosylase, YtkR2, that serves as a self-resistance mechanism against yatakemycin toxicity. We previously reported that AlkD, which is not present in an SCPCHD producer, provides only limited resistance against yatakemycin. We now show that YtkR2 and C10R5, a previously uncharacterized homolog found in the CC-1065 biosynthetic gene cluster ofStreptomyces zelensis, confer far greater resistance against their respective SCPCHD natural products. We identify a structural basis for substrate specificity across gene clusters and show a correlation between in vivo resistance and in vitro enzymatic activity indicating that reduced product affinity—not enhanced substrate recognition—is the evolutionary outcome of selective pressure to provide self-resistance against yatakemycin and CC-1065.

    

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4. Time-Resolved Vibrational Fingerprints for Two Silver Cluster-DNA Fluorophores

   Y. Zhang, C. He ( October 2020 , The journal of physical chemistry letters)

   DNA-templated silver clusters are chromophores in which the nucleobases encode the cluster spectra and brightness. We describe the coordination environments of two nearly identical Ag106+ clusters that form with 18-nucleotide strands CCCCA CCCCT CCCX TTTT, with X = guanosine and inosine. For the first time, femtosecond time-resolved infrared (TRIR) spectroscopy with visible excitation and mid-infrared probing is used to correlate the response of nucleobase vibrational modes to electronic excitation of the metal cluster. A rich pattern of transient TRIR peaks in the 1400–1720 cm–1 range decays synchronously with the visible emission. Specific infrared signatures associated with the single guanosine/inosine along with a subset of cytidines, but not the thymidines, are observed. These fingerprints suggest that the network of bonds between a silver cluster adduct and its polydentate DNA ligands can be deciphered to rationally tune the coordination and thus spectra of molecular silver chromophores. 

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5. A Tissue Comparison of DNA Methylation of the Glucocorticoid Receptor Gene (Nr3c1) in European Starlings

   https://doi.org/10.1093/icb/icz034  

   Siller, Stefanie J ; Rubenstein, Dustin R ( June 2019 , Integrative and Comparative Biology)

   Abstract Negative feedback of the vertebrate stress response via the hypothalamic–pituitary–adrenal (HPA) axis is regulated by glucocorticoid receptors in the brain. Epigenetic modification of the glucocorticoid receptor gene (Nr3c1), including DNA methylation of the promoter region, can influence expression of these receptors, impacting behavior, physiology, and fitness. However, we still know little about the long-term effects of these modifications on fitness. To better understand these fitness effects, we must first develop a non-lethal method to assess DNA methylation in the brain that allows for multiple measurements throughout an organism’s lifetime. In this study, we aimed to determine if blood is a viable biomarker for Nr3c1 DNA methylation in two brain regions (hippocampus and hypothalamus) in adult European starlings (Sturnus vulgaris). We found that DNA methylation of CpG sites in the complete Nr3c1 putative promoter varied among tissue types and was lowest in blood. Although we identified a similar cluster of correlated Nr3c1 putative promoter CpG sites within each tissue, this cluster did not show any correlation in DNA methylation among tissues. Additional studies should consider the role of the developmental environment in producing epigenetic modifications in different tissues. 

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