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2'- -ribose methylation of the first transcribed base (adenine or A in SARS-CoV-2) of viral RNA mimics the host RNAs and subverts the innate immune response. How nsp16, with its obligate partner nsp10, assembles on the 5'-end of SARS-CoV-2 mRNA to methylate the A has not been fully understood. We present a ∼ 2.
View Article and Find Full Text PDFIn duplex DNA, A-T and G-C form Watson-Crick base pairs, and Hoogsteen pairing only dominates upon protein binding or DNA damage. Using NMR, we show that an A-T Hoogsteen base pair previously observed in crystal structures of transposon DNA hairpins bound to TnpA protein forms in solution even in the absence of TnpA. This Hoogsteen base pair, located adjacent to a dinucleotide apical loop, exists in dynamic equilibrium with a minor Watson-Crick conformation (population ∼11% and lifetime ∼55 µs).
View Article and Find Full Text PDFUnlabelled: Bactofilins are a recently discovered class of cytoskeletal protein, widely implicated in subcellular organization and morphogenesis in bacteria and archaea. Several lines of evidence suggest that bactofilins polymerize into filaments using a central β-helical core domain, flanked by variable N- and C-terminal domains that may be important for scaffolding and other functions. However, a systematic exploration of the characteristics of these domains has yet to be performed.
View Article and Find Full Text PDFAs the toolbox of base editors (BEs) expands, selecting appropriate BE and guide RNA (gRNA) to achieve optimal editing efficiency and outcome for a given target becomes challenging. Here, we construct a set of 10 adenine and cytosine BEs with high activity and broad targeting scope, and comprehensively evaluate their editing profiles and properties head-to-head with 34,040 BE-gRNA-target combinations using genomically integrated long targets and tiling gRNA strategies. Interestingly, we observe widespread non-canonical protospacer adjacent motifs (PAMs) for these BEs.
View Article and Find Full Text PDFStructural and Functional Insights into UDGs.
Protein Pept Lett
December 2024
Department of Biotechnology, Jaypee Institute of Information Technology, A-10 Sec 62, Noida, 201309, India.
Endogenous or exogenous DNA damage needs to be repaired, therefore, cells in all the three domains have repair pathways to maintain the integrity of their genetic material. Uracil DNA glycosylases (UDGs), also known as UNGs (uracil-DNA N-glycosylases), are part of the base-excision repair (BER) pathway. These enzymes specifically remove uracil from DNA molecules by cleaving the glycosidic bond between the uracil base and the deoxyribose sugar.
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