Coacervates are dense aqueous phases that form by liquid-liquid phase separation. Seven Pt(II) complexes with different charges and nucleotide reactivities were examined for their ability to induce co Show more
Coacervates are dense aqueous phases that form by liquid-liquid phase separation. Seven Pt(II) complexes with different charges and nucleotide reactivities were examined for their ability to induce coacervate formation in a 21-mer single-stranded DNA (ssDNA). Only AMPZ ([cis-{Pt(NH3)2}2(ÎŒ-pyrazolato)(ÎŒ-OH)](NO3)2), a cationic dinuclear Pt(II) complex, efficiently induced coacervate formation in ssDNA containing only thymine (T21-DNA). AMPZ has very low reactivity with thymine but relatively high reactivity with guanine, and when three of the thymines in T21-DNA were substituted with a guanine to produce T18-G3-DNA, the resulting coacervate was observed to undergo gelation via the formation of an extensive Pt-DNA coordination-bonded network. We then examined the construction of coacervates that comprise multiple phases by adding AMPZ to a mixture of two types of ssDNAs, a highly reactive T10-G11-DNA and a minimally reactive T21-DNA, and found that two distinct assembly statesâa cell mimetic assembly and a DNA-encapsulating gelâcould be formed. Show less
Abstract TFIIH is a 10âsubunit complex that regulates RNA polymerase II (pol II) transcription but also serves other important biological roles. Although much remains unknown about TFIIH function in Show more
Abstract TFIIH is a 10âsubunit complex that regulates RNA polymerase II (pol II) transcription but also serves other important biological roles. Although much remains unknown about TFIIH function in eukaryotic cells, much progress has been made even in just the past few years, due in part to technological advances (e.g. cryoEM and single molecule methods) and the development of chemical inhibitors of TFIIH enzymes. This review focuses on the major cellular roles for TFIIH, with an emphasis on TFIIH function as a regulator of pol II transcription. We describe the structure of TFIIH and its roles in pol II initiation, promoterâproximal pausing, elongation, and termination. We also discuss cellular roles for TFIIH beyond transcription (e.g. DNA repair, cell cycle regulation) and summarize small molecule inhibitors of TFIIH and diseases associated with defects in TFIIH structure and function. Show less
Abstract Significance: Mitochondria are the energetic, metabolic, redox, and information signaling centers of the cell. Substrate pressure, mitochondrial network dynamics, and cristae morphology Show more
Abstract Significance: Mitochondria are the energetic, metabolic, redox, and information signaling centers of the cell. Substrate pressure, mitochondrial network dynamics, and cristae morphology state are integrated by the protonmotive force Î p or its potential component, ΠΚ , which are attenuated by proton backflux into the matrix, termed uncoupling. The mitochondrial uncoupling proteins (UCP1â5) play an eminent role in the regulation of each of the mentioned aspects, being involved in numerous physiological events including redox signaling. Recent Advances: UCP2 structure, including purine nucleotide and fatty acid (FA) binding sites, strongly support the FA cycling mechanism: UCP2 expels FA anions, whereas uncoupling is achieved by the membrane backflux of protonated FA. Nascent FAs, cleaved by phospholipases, are preferential. The resulting Î p dissipation decreases superoxide formation dependent on Î p . UCP-mediated antioxidant protection and its impairment are expected to play a major role in cell physiology and pathology. Moreover, UCP2-mediated aspartate, oxaloacetate, and malate antiport with phosphate is expected to alter metabolism of cancer cells. Critical Issues: A wide range of UCP antioxidant effects and participations in redox signaling have been reported; however, mechanisms of UCP activation are still debated. Switching off/on the UCP2 protonophoretic function might serve as redox signaling either by employing/releasing the extra capacity of cell antioxidant systems or by directly increasing/decreasing mitochondrial superoxide sources. Rapid UCP2 degradation, FA levels, elevation of purine nucleotides, decreased Mg 2+ , or increased pyruvate accumulation may initiate UCP-mediated redox signaling. Future Directions: Issues such as UCP2 participation in glucose sensing, neuronal (synaptic) function, and immune cell activation should be elucidated. Antioxid. Redox Signal. 29, 667â714. Show less