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- Sciencedirect from 1997, Proquest, Rcgp, Gale, CSA, and Ingenta
Top3-rmi1 dissolve rad51-mediated d loops by a topoisomerase-based mechanism.
We report that D loops can also be disrupted by DNA topoisomerase 3 (Top3), and this disruption depends on Top3's catalytic activity. Yeast Top3 specifically disrupts D loops mediated by yeast Rad51/Rad54; protein-free D loops or D loop mediated by bacterial RecA protein or human RAD51/RAD54 resist...
Innate antiviral host defense attenuates TGF-β function through IRF3-mediated suppression of Smad signaling.
We found that RLR signaling represses TGF-β responses. This regulation is mediated by activated IRF3, using a dual mechanism of IRF3-directed suppression. Activated IRF3 interacts with Smad3, thus inhibiting TGF-β-induced Smad3 activation and, in the nucleus, disrupts functional Smad3 transcription...
The yeast ER-intramembrane protease Ypf1 refines nutrient sensing by regulating transporter abundance.
We named yeast presenilin fold 1 (Ypf1), which we verify to be an SPP-type protease that localizes to the endoplasmic reticulum (ER). Our work shows that Ypf1 functionally interacts with the ER-associated degradation (ERAD) factors Dfm1 and Doa10 to regulate the abundance of nutrient transporters by...
Pores of no return.
In this issue, Bleicken et al. (2014) use double electron-electron resonance (DEER) spectroscopy to propose a new model for the active form of Bax at membranes that differs significantly from those previously proposed. Copyright © 2014 Elsevier Inc. All rights reserved.
Ribosomes left in the dust: diverse strategies for Peptide-mediated translation stalling.
In two recent papers, Arenz et al. (2014a) and Bischoff et al. (2014) provide structural insights into drug-induced, peptide-mediated stalling of the ribosome. Copyright © 2014 Elsevier Inc. All rights reserved.
NF-κB directs dynamic super enhancer formation in inflammation and atherogenesis.
We characterized the dynamics, structure, and function of regulatory elements in the activated endothelial cell epigenome. Stimulation with tumor necrosis factor alpha prompted a dramatic and rapid global redistribution of chromatin activators to massive de novo clustered enhancer domains. Inflammat...
Mechanism of DNA methylation-directed histone methylation by KRYPTONITE.
We report on the structure of KYP in complex with methylated DNA, substrate H3 peptide, and cofactor SAH, thereby defining the spatial positioning of the SRA domain relative to the SET domain. The methylated DNA is bound by the SRA domain with the 5mC flipped out of the DNA, while the H3(1-15) pepti...
Tracing compartmentalized NADPH metabolism in the cytosol and mitochondria of mammalian cells.
We develop an approach to resolve NADP(H)-dependent pathways present within both the cytosol and the mitochondria. By tracing hydrogen in compartmentalized reactions that use NADPH as a cofactor, including the production of 2-hydroxyglutarate by mutant isocitrate dehydrogenase enzymes, we can observ...
Directed network wiring identifies a key protein interaction in embryonic stem cell differentiation.
We designed variants of the Grb2 SH2 domain ("pY-clamps") whose specificity is highly biased toward a single phosphotyrosine (pY) motif among many potential pYXNX Grb2-binding sites. Surprisingly, directing Grb2 predominantly to a single pY site of the Ptpn11/Shp2 phosphatase, but not other sites te...
Multiplexed and programmable regulation of gene networks with an integrated RNA and CRISPR/Cas toolkit in human cells.
We present new strategies that enable expression of functional gRNAs from RNA polymerase II promoters and multiplexed production of proteins and gRNAs from a single transcript in human cells. We use multiple RNA regulatory strategies, including RNA-triple-helix structures, introns, microRNAs, and ri...