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Showing results 1 to 4 of 4

Ebooks (Sách điện tử)

Cas4/1 dual nuclease activities enable prespacer maturation and directional integration in a type I-G CRISPR-Cas system

Authors : Dhingra, Yukti (2023)

CRISPR-Cas adaptive immune systems uptake short ‘spacer’ sequences from foreign DNA and 8 incorporate them into the host genome to serve as templates for crRNAs that guide interference 9 against future infections. Adaptation in CRISPR systems is mediated by Cas1-Cas2 complexes 10 that catalyze integration of prespacer substrates into the CRISPR array. Many DNA targeting 11 systems also require Cas4 endonucleases for functional spacer acquisition. Cas4 selects...

Journal article

Genetic screening identifies integrated stress response kinase HRI (EIF2AK1) as a negative regulator of PINK1 and mitophagy signalling

Authors : Singh, Pawan Kishor (2023)

Loss of function mutations of the PINK1 kinase cause familial early-onset Parkinson’s disease. PINK1 is activated upon mitochondrial damage to phosphorylate Ubiquitin and Parkin to trigger removal of damaged mitochondria by autophagy (mitophagy). PINK1 also indirectly phosphorylates a subset of Rab GTPases including Rab8A. We have performed a siRNA screen of all human Ser/Thr kinases in HeLa cells and discovered the integrated stress respo...

Journal article

PAM binding ensures orientational integration during Cas4-Cas1-Cas2 mediated CRISPR adaptation

Authors : Dhingra, Yukti (2023)

Adaptation in CRISPR-Cas systems immunizes bacteria and archaea against mobile genetic 10 elements. In many DNA-targeting systems, the Cas4-Cas1-Cas2 complex is required for selection 11 and processing of DNA segments containing PAM sequences, prior to integration of these 12 “prespacer” substrates as spacers in the CRISPR array. We determined cryo-EM structures of the 13 Cas4-Cas1-Cas2 adaptation complex from the type I-C system that encodes st...

Journal article

System-wide profiling by proteome integral solubility alteration assay of drug residence times for target characterization

Authors : Sabatier, Pierre (2023)

Most drugs used in the clinic and drug candidates target multiple proteins, and thus detailed characterization of their efficacy targets is required. While current methods rely on quantitative measurements at thermodynamic equilibrium, kinetic parameters such as the residence time of a drug on its target provide a better proxy for efficacy in vivo. Here, we present Residence Time Proteome Integral Solubility Alteration (ResT-PISA) assay which provides monitor...