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  1. Altered DNA dynamics at lesion sites are implicated in how DNA repair proteins pause and identify damage within genomic DNA. We examined DNA dynamics in the context of damage recognition by Rad4 (yeast ortholog of XPC), which recognizes diverse lesions from environmental mutagens and initiates nucleotide excision repair. Previous studies with a cytosine-analog FRET pair placed on either side of 3 base-pair (bp) mismatched sites – recognized specifically by Rad4 in vitro – unveiled severely deformed DNA even without Rad4 (Chakraborty et al. (2018) Nucleic Acid Res. 46: 1240-1255). Here, using laser T-jump, we revealed the timescales of these spontaneous deformations. 3-bp AT-rich nonspecific sites, whether matched or mismatched, exhibited conformational dynamics primarily within the T-jump observation window (~20 µs – <100 ms), albeit with some amplitude in unresolved (<20 µs) kinetics. The amplitudes of the “missing” fast kinetics increased dramatically for mismatched specific sites, which were further distinguished by additional “missing” amplitude in slow (>100 ms) kinetics at elevated temperatures. We posit that the rapid (µs-ms) fluctuations help stall a diffusing protein at AT-rich/damaged sites and that the >100-ms kinetics reflect a propensity for specific DNA to adopt unwound/bent conformations that may resemble Rad4-bound structures. These studies provide compelling evidence for unusual DNA dynamics and deformability that likely govern how Rad4 senses DNA damage. 
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    Free, publicly-accessible full text available April 3, 2025
  2. null (Ed.)
  3. Abstract

    The importance of lightning has long been recognized from the point of view of climate‐related phenomena. However, the detailed investigation of lightning on global scales is currently hindered by the incomplete and spatially uneven detection efficiency of ground‐based global lightning detection networks and by the restricted spatio‐temporal coverage of satellite observations. We are developing different methods for investigating global lightning activity based on Schumann resonance (SR) measurements. SRs are global electromagnetic resonances of the Earth‐ionosphere cavity maintained by the vertical component of lightning. Since charge separation in thunderstorms is gravity‐driven, charge is typically separated vertically in thunderclouds, so every lightning flash contributes to the measured SR field. This circumstance makes SR measurements very suitable for climate‐related investigations. In this study, 19 days of global lightning activity in January 2019 are analyzed based on SR intensity records from 18 SR stations and the results are compared with independent lightning observations provided by ground‐based (WWLLN, GLD360, and ENTLN) and satellite‐based (GLM, LIS/OTD) global lightning detection. Daily average SR intensity records from different stations exhibit strong similarity in the investigated time interval. The inferred intensity of global lightning activity varies by a factor of 2–3 on the time scale of 3–5 days which we attribute to continental‐scale temperature changes related to cold air outbreaks from polar regions. While our results demonstrate that the SR phenomenon is a powerful tool to investigate global lightning, it is also clear that currently available technology limits the detailed quantitative evaluation of lightning activity on continental scales.

     
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