The use of light to mediate controlled radical polymerization has emerged as a powerful strategy for rational polymer synthesis and advanced materials fabrication. This review provides a comprehensive survey of photocontrolled, living radical polymerizations (photo-CRPs). From the perspective of mechanism, all known photo-CRPs are divided into either (1) intramolecular photochemical processes or (2) photoredox processes. Within these mechanistic regimes, a large number of methods are summarized and further classified into subcategories based on the specific reagents, catalysts, etc., involved. To provide a clear understanding of each subcategory, reaction mechanisms are discussed. In addition, applications of photo-CRP reported so far, which include surface fabrication, particle preparation, photoresponsive gel design, and continuous flow technology, are summarized. We hope this review will not only provide informative knowledge to researchers in this field but also stimulate new ideas and applications to further advance photocontrolled reactions.

DNA polymerases copy DNA templates with remarkably high fidelity, checking for correct base-pair formation both at nucleotide insertion and at subsequent DNA extension steps. Despite extensive biochemical, genetic and structural studies, the mechanism by which nucleotides are correctly incorporated is not known. Here we present high-resolution crystal structures of a thermostable bacterial (Bacillus stearothermophilus) DNA polymerase I large fragments with DNA primer templates bound productively at the polymerase active site. The active site retains catalytic activity, allowing direct observation of the products of several rounds of nucleotide incorporation. The polymerase also retains its ability to discriminate between correct and incorrectly paired nucleotides in the crystal. Comparison of the structures of successively translocated complexes allows the structural features for the sequence-independent molecular recognition of correctly formed base pairs to be deduced unambiguously. These include extensive interactions with the first four to five base pairs in the minor groove, location of the terminal base pair in a pocket of excellent steric complementarity favouring correct base-pair formation, and a conformational switch from B-form to underwound A-form DNA at the polymerase active site.

SIRT3 is a major mitochondrial NAD؉ -dependent protein deacetylase playing important roles in regulating mitochondrial metabolism and energy production and has been linked to the beneficial effects of exercise and caloric restriction. SIRT3 is emerging as a potential therapeutic target to treat metabolic and neurological diseases. We report the first sets of crystal structures of human SIRT3, an apo-structure with no substrate, a structure with a peptide containing acetyl lysine of its natural substrate acetyl-CoA synthetase 2, a reaction intermediate structure trapped by a thioacetyl peptide, and a structure with the dethioacetylated peptide bound. These structures provide insights into the conformational changes induced by the two substrates required for the reaction, the acetylated substrate peptide and NAD ؉ . In addition, the binding study by isothermal titration calorimetry suggests that the acetylated peptide is the first substrate to bind to SIRT3, before NAD ؉ . These structures and biophysical studies provide key insight into the structural and functional relationship of the SIRT3 deacetylation activity.Sirtuins are class III histone deacetylases that couple lysine deacetylation with NAD ϩ hydrolysis and are highly conserved in prokaryotes and eukaryotes (1). Mammals possess seven sirtuins, SIRT1-7, that occupy different subcellular compartments such as the nucleus (SIRT1, -6, -7), cytoplasm (SIRT2), and the mitochondria (SIRT3, -4, and -5) (2). They deacetylate lysines not only on histone substrates (3, 4) but also on nonhistone substrates such as p53 tumor suppressor protein (5), Foxo transcription factors (6, 7), PGC-1␣ (8), ␣-tubulin (9), acetyl-CoA synthetases (10 -12), and glutamate dehydrogenase (13). SIRT4 and SIRT6 have been shown to have ADP-ribosyltransferase activity (14 -16). Sirtuins have been reported to play important roles in gene silencing (17), cell cycle regulation (18,19), metabolism (8, 10 -12, 14, 20 -22), apoptosis (5, 23, 24), the lifespan-extension effects of calorie restriction (25,26), and circadian rhythms (27)(28)(29)(30) (50), and SIRT5 (51). Sirtuins contain a conserved enzymatic core with two domains; that is, a large Rossmann fold domain that binds NAD ϩ and a small domain formed by two insertions of the large domain that binds to a zinc atom. The acetylated peptide substrate binds to the cleft between the two domains. Some of the known structures are apo structures with sirtuin protein alone, whereas others are bound to acetylated peptide substrate and/or NAD ϩ and its analogs. These structures revealed the mechanism of action for the deacetylation activity and substrate specificity.SIRT3 localizes in mitochondria (13, 52-54) and is a major mitochondrial deacetylase. Hyperacetylation of mitochondrial proteins have been observed in SIRT3 knock-out mice (13, 55). Several key enzymes involved in energy production in the mitochondria have been identified as SIRT3 substrates. Acetyl-CoA synthetase 2 (AceCS2) 2 converts acetate into acetyl-CoA in the mitochondria. Deacetyla...