The postreplicative mismatch repair (MMR) is an almost ubiquitous DNA repair essential for maintaining genome stability. It has been suggested that have an alternative MMR in which NucS, an endonuclease with no structural homology to the canonical MMR proteins (MutS/MutL), is the key factor. Here, we analyze the spontaneous mutations accumulated in a neutral manner over thousands of generations by and its MMR-deficient derivative (Δ). The base pair substitution rates per genome per generation are 0.004 and 0.165 for wild type and Δ, respectively. By comparing the activity of different bacterial MMR pathways, we demonstrate that both MutS/L- and NucS-based systems display similar specificity and mutagenesis bias, revealing a functional evolutionary convergence. However, NucS is not able to repair indels in vivo. Our results provide an unparalleled view of how this mycobacterial system works in vivo to maintain genome stability and how it may affect evolution.
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http://dx.doi.org/10.1126/sciadv.aay4453 | DOI Listing |
ACS Chem Biol
January 2025
Department of Chemistry, Stony Brook University, Stony Brook, New York 11794-3400, United States.
OaPAC, the photoactivated adenylyl cyclase from , is composed of a blue light using FAD (BLUF) domain fused to an adenylate cyclase (AC) domain. Since both the BLUF and AC domains are part of the same protein, OaPAC is a model for understanding how the ultrafast modulation of the chromophore binding pocket caused by photoexcitation results in the activation of the output domain on the μs-s time scale. In the present work, we use unnatural amino acid mutagenesis to identify specific sites in the protein that are involved in transducing the signal from the FAD binding site to the ATP binding site.
View Article and Find Full Text PDFNat Commun
January 2025
Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston Salem, NC, USA.
Microbial species must compete for space and nutrients to persist in the gastrointestinal (GI) tract, and our understanding of the complex pathobiont-microbiota interactions is far from complete. Klebsiella pneumoniae, a problematic, often drug-resistant nosocomial pathogen, can colonize the GI tract asymptomatically, serving as an infection reservoir. To provide insight on how K.
View Article and Find Full Text PDFBMJ Case Rep
January 2025
Department of Internal Medicine, University of Kentucky, Lexington, Kentucky, USA.
BCR::ABL1-like B-lymphoblastic leukaemia (B-ALL) neoplasms lack the BCR::ABL1 translocation but have a gene expression profile like BCR::ABL1 positive B-ALL. This includes alterations in cytokine receptors and signalling genes, such as and Cases with CRLF2 rearrangements account for approximately 50% of cases of Philadelphia-like acute lymphoblastic leukaemia (Ph-like ALL), and the frequency of specific genomic lesions varies with ethnicity such that IGH::CRLF2 translocations are more common in Hispanics and Native Americans.We report two cases of BCR::ABL1-like ALL, with significant eosinophilia.
View Article and Find Full Text PDFBiochem Biophys Res Commun
January 2025
Department of Biology, Chosun University, Gwangju, 61452, Republic of Korea. Electronic address:
Plant Toll/interleukin-1 receptor (TIR) domains function as NADases and ribosyl-transferases generating second messengers that trigger hypersensitive responses. TIR-X (TX) proteins contain a TIR domain with or without various C-terminal domains and lack the canonical nucleotide-binding site and leucine-rich repeat domain. In a previous study, we identified an Arabidopsis thaliana activation-tagging line with severe growth defects caused by the overexpression of the AtTX12 gene.
View Article and Find Full Text PDFJ Virol
January 2025
Research Center for Swine Diseases, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China.
Unlabelled: Porcine deltacoronavirus (PDCoV) is an enteric pathogen that burdens the global pig industry and is a public health concern. The development of effective antiviral therapies is necessary for the prevention and control of PDCoV, yet to date, there are few studies on the therapeutic potential of PDCoV-neutralizing antibodies. Here, we investigate the therapeutic potential of a novel monoclonal antibody (mAb 4A6) which targets the PDCoV S1 protein and effectively neutralizes PDCoV, both pre- and post-attachment on cells, with IC50 values of 0.
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