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  1. Transcription-coupled nucleotide excision repair (TC-NER) is a highly conserved DNA repair pathway that removes bulky lesions in the transcribed genome. Cockayne syndrome B protein (CSB), or its yeast ortholog Rad26, has been known for decades to play important roles in the lesion-recognition steps of TC-NER. Another conserved protein ELOF1, or its yeast ortholog Elf1, was recently identified as a core transcription-coupled repair factor. How Rad26 distinguishes between RNA polymerase II (Pol II) stalled at a DNA lesion or other obstacles and what role Elf1 plays in this process remains unknown. Here, we present cryo-EM structures of Pol II-Rad26 complexes stalled at different obstacles that show that Rad26 uses a common mechanism to recognize a stalled Pol II, with additional interactions when Pol II is arrested at a lesion. A cryo-EM structure of lesion-arrested Pol II-Rad26 bound to Elf1 revealed that Elf1 induces further interactions between Rad26 and a lesion-arrested Pol II. Biochemical and genetic data support the importance of the interplay between Elf1 and Rad26 in TC-NER initiation. Together, our results provide important mechanistic insights into how two conserved transcription-coupled repair factors, Rad26/CSB and Elf1/ELOF1, work together at the initial lesion recognition steps of transcription-coupled repair.

     
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    Free, publicly-accessible full text available January 16, 2025
  2. Abstract

    Artificially Expanded Genetic Information Systems (AEGIS) add independently replicable unnatural nucleotide pairs to the natural G:C and A:T/U pairs found in native DNA, joining the unnatural pairs through alternative modes of hydrogen bonding. Whether and how AEGIS pairs are recognized and processed by multi-subunit cellular RNA polymerases (RNAPs) remains unknown. Here, we show thatE. coliRNAP selectively recognizes unnatural nucleobases in a six-letter expanded genetic system. High-resolution cryo-EM structures of three RNAP elongation complexes containing template-substrate UBPs reveal the shared principles behind the recognition of AEGIS and natural base pairs. In these structures, RNAPs are captured in an active state, poised to perform the chemistry step. At this point, the unnatural base pair adopts a Watson-Crick geometry, and the trigger loop is folded into an active conformation, indicating that the mechanistic principles underlying recognition and incorporation of natural base pairs also apply to AEGIS unnatural base pairs. These data validate the design philosophy of AEGIS unnatural basepairs. Further, we provide structural evidence supporting a long-standing hypothesis that pair mismatch during transcription occurs via tautomerization. Together, our work highlights the importance of Watson-Crick complementarity underlying the design principles of AEGIS base pair recognition.

     
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  3. Abstract

    Tri‐cation (Cs+/CH3NH3+/CH(NH2)2+) and dual‐anion (Br/I) perovskites are promising light absorbers for inexpensive infrared (IR) photodetectors but degrade under prolonged IR exposure. Here, stable IR photodetectors based on electrospun tri‐cation perovskite fibers infiltrated with hole‐transporting π‐conjugated small molecule 2,2′,7,7′‐tetrakis[N,N‐di(4‐methoxyphenyl)amino]‐9,9‐spirobifluorene (Spiro‐OMeTAD) are demonstrated. These hybrid perovskite photodetectors operate at a low bias of 5 V and exhibit ultra‐high gains with external quantum efficiencies (EQEs) as high as 3009%, decreasing slightly to ≈2770% after 3 months in air. These EQE values are almost ten times larger than those measured for photodetectors comprising bilayer perovskite/Spiro‐OMeTAD films. A high density of charge traps on electrospun fiber surfaces gives rise to a photomultiplication effect in which photogenerated holes can travel through the active layer multiple times before recombining with trapped electrons. Time‐resolved photoluminescence and conductive atomic force microscopy mapping reveal the improved performance of electrospun fibers to originate from the significantly enhanced interfacial surface area between the perovskite and Spiro‐OMeTAD compared to bilayers. As a solution‐based, scalable and continuous method of depositing perovskite layers, electrospinning thus presents a promising strategy for the inexpensive fabrication of high‐performance IR photodetectors for applications ranging from information technology to imaging.

     
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