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Creators/Authors contains: "Sharma, Pankaj"

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  1. Abstract

    The N-(2-deoxy-d-erythro-pentofuranosyl)-urea DNA lesion forms following hydrolytic fragmentation of cis-5R,6S- and trans-5R,6R-dihydroxy-5,6-dihydrothymidine (thymine glycol, Tg) or from oxidation of 7,8-dihydro-8-oxo-deoxyguanosine (8-oxodG) and subsequent hydrolysis. It interconverts between α and β deoxyribose anomers. Synthetic oligodeoxynucleotides containing this adduct are efficiently incised by unedited (K242) and edited (R242) forms of the hNEIL1 glycosylase. The structure of a complex between the active site unedited mutant CΔ100 P2G hNEIL1 (K242) glycosylase and double-stranded (ds) DNA containing a urea lesion reveals a pre-cleavage intermediate, in which the Gly2 N-terminal amine forms a conjugate with the deoxyribose C1′ of the lesion, with the urea moiety remaining intact. This structure supports a proposed catalytic mechanism in which Glu3-mediated protonation of O4′ facilitates attack at deoxyribose C1′. The deoxyribose is in the ring-opened configuration with the O4′ oxygen protonated. The electron density of Lys242 suggests the ‘residue 242-in conformation’ associated with catalysis. This complex likely arises because the proton transfer steps involving Glu6 and Lys242 are hindered due to Glu6-mediated H-bonding with the Gly2 and the urea lesion. Consistent with crystallographic data, biochemical analyses show that the CΔ100 P2G hNEIL1 (K242) glycosylase exhibits a residual activity against urea-containing dsDNA.

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  2. Ferroelectric field‐effect transistors (FeFETs) employing graphene on inorganic perovskite substrates receive considerable attention due to their interesting electronic and memory properties. They are known to exhibit an unusual hysteresis of electronic transport that is not consistent with the ferroelectric polarization hysteresis and is previously shown to be associated with charge trapping at graphene–ferroelectric interface. Here, an electrical measurement scheme that minimizes the effect of charge traps and reveals the polarization‐dependent hysteresis of electronic transport in graphene–Pb(Zr,Ti)O3FeFETs is demonstrated. Observation of the polarization‐dependent conductivity hysteresis is important for the fundamental understanding of the interplay between the ferroelectric polarization and charge carriers in graphene. It is also important for practical memory applications because this hysteresis emulates the operation of nonvolatile memories and reveals the range of ON and OFF currents that can be achieved in long term data storage. It is demonstrated that this measurement scheme can be used to optimize the memory performance of graphene–PZT FeFETs that can exhibit nonvolatile time‐independent ON/OFF ratios of over 5. The described measurement technique can potentially be used in the studies of kinetics of charge trap dissipation, polarization‐dependent properties, and memory performance of FeFET devices comprising other 2D materials and various ferroelectric substrates.

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