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Discoveries Category

Controling RNA Polymerase Dynamics

Mar. 22, 2019—The process of transcription is extremely complex, requiring the well-coordinated interactions of numerous modulatory proteins and protein complexes. Two key players in this process are cyclin-dependent kinase (CDK)7 and CDK9, both of which phosphorylate multiple sites on RNA polymerase II (Pol II), the primary protein responsible for transcription in eukaryotes, as well as on other...

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Targeting the WIN Site of WDR5

Mar. 21, 2019—WDR5 serves as a scaffold for protein complexes containing epigenetic “writers” that catalyze histone modification reactions. Among the WDR5-dependent complexes are those encompassing MLL/SET-type histone methyltransferases (HMTs) responsible for di- and trimethylation of histone 3 at lysine-4 (H3K4). WDR5 contains a WIN (WDR interaction) site, which binds to an arginine-containing WIN motif on other proteins...

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In Search of Synergy

Mar. 15, 2019—In recent years, the number of complex diseases such as cancer and drug resistant infections that are treated with multiple drugs has rapidly increased. Through combining drugs, one hopes to obtain synergy either by increasing potency (so the desired effect can be achieved with lower drug doses) or increasing efficacy (so greater maximum effect can...

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Activation of ATR for Distinct Signaling Functions

Feb. 20, 2019—ATR (ataxia telangiectasia-mutated and Rad3-related) is a kinase well known for its role in the DNA damage and replication stress responses; however, it also is an important modulator of the cell cycle and mitosis. In mammalian cells, activation of ATR is mediated by two proteins, ETAA1 and TOPBP1, both of which associate with the kinase...

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Key to Islet Cell Differentiation

Jan. 31, 2019—The pancreatic islets of Langerhans are specialized structures containing five distinct types of cells, (α, β, γ, δ, ε), each of which secretes a different hormone (glucagon, insulin, pancreatic polypeptide, somatostatin, and ghrelin, respectively). Understanding the mechanisms that determine the total and relative quantities of these five islet cell types is key to understanding diabetes,...

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Targeting Proteins for Endocytosis

Jan. 23, 2019—One mechanism that cells use to modulate the activity of plasma membrane proteins is to remove them from the surface through endocytosis. However, this mechanism requires that proteins to be removed are correctly identified so that needed membrane functions are not compromised. Ubiquitylation is one way that cells label plasma membrane proteins for endocytosis, though...

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Amplifying the Signal with a Scaffold

Jan. 14, 2019—Scaffolding proteins serve as sites of binding and organization for the multiple components involved in many signaling pathways. Scaffolding promotes key protein-protein interactions and can substantially amplify a signal; however, if proteins are bound too tightly to a scaffold, signal propagation may actually be hindered. The precise mechanisms that regulate the interactions between scaffolding proteins...

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The Fine Points of Exocyst Dynamics

Dec. 17, 2018—Exocytic vesicles fuse with the plasma membrane (PM) through the action of SNARE proteins, which in turn, are delivered to the vesicles by multisubunit protein tethering complexes. One such complex is the exocyst, comprising two tetrameric subcomplexes, SC1 (composed of SEC3, SEC5, SEC6, and SEC8) and SC2 (composed of SEC10, SEC15, EXO70, and EXO84). Prior...

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Keys to Sarcomere Assembly

Dec. 17, 2018—The sarcomere is a repeating unit of interdigitating actin and myosin filaments that serves as the building blocks of the myofibrils in striated muscle cells. Sarcomeres are demarcated at each end by a Z-disc containing α-actinin 2 to which thin fibers of actin are attached. In the center are the A-bands comprising thick filaments composed...

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HMCES: A New Guardian Against DNA Damage

Dec. 14, 2018—In DNA, abasic sites (apurinic/apyrimidinic or AP sites) occur through spontaneous hydrolysis of the glycosidic bond that joins the base to the deoxyribose ring (a common reaction following formation of some kinds of DNA adducts) or through the action of DNA glycosylases during repair of damaged bases. In double-stranded DNA, AP sites are easily repaired...

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