= Robert Silber
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= R. Silber
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{synonym}
Robert Silber is a researcher credited with early characterization of <RNA ligases>. His full name and New York University medicine affiliation appear on the original 1972 article, although the indexed citation abbreviates the byline as R. Silber.<Purification and properties of bacteriophage T4-induced RNA ligase by R. Silber and others>[Original full byline and author affiliation; PNAS 69, 3009–3013]{ref}
Silber and collaborators investigated an <RNA ligase> from phage-infected <Escherichia coli>. The purified <enzyme> converted labelled terminal <phosphate> groups into internal <phosphodiester bonds>, requiring <ATP> and <magnesium>. Resistance to <alkaline phosphatase>, together with tests using <exonucleases>, supported joining the two ends of an individual <RNA> chain to produce <circular RNA> under the studied conditions.<Purification and properties of bacteriophage T4-induced RNA ligase by R. Silber and others>[Abstract: ATP/Mg dependence, protected end label and exonuclease evidence for intramolecular circularization]{ref}
The experiment illustrates why several chemical observations are needed to establish molecular topology. A label no longer accessible at a chain end suggests a change in its chemical setting, but that result alone does not determine whether two different molecules joined or one molecule closed on itself.
An original counting model makes the ambiguity precise. Begin with $100$ linear chains, each with two free ends, giving $200$ ends. Closing $40$ chains into separate rings leaves $60$ linear chains, $120$ free ends and $100$ total molecules. Alternatively, joining $40$ disjoint pairs into longer linear chains leaves $60$ molecules, again with $120$ free ends. The same reduction in end count can therefore accompany different molecular products. These are invented counts, not the paper's measurements; additional chemical and size information is needed to distinguish the products.
The historical inference combined the protected label with evidence that the product lacked accessible opposite ends. It was an inference about the tested <RNA> substrate and assay, not a claim that every <RNA ligase> reaction always creates a circle.<Purification and properties of bacteriophage T4-induced RNA ligase by R. Silber and others>[Abstract: poly(A) substrate, no detected intermolecular reaction and circular-product interpretation]{ref}
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