The DNA of all organisms is constantly damaged by exogenous and endogenous agents. Base excision repair (BER) is important for the removal of several non-bulky lesions from the DNA, however not much is known about the contributions of other DNA repair pathways to the processing of non-bulky lesions. Here we utilized a luciferase reporter system to assess the contributions of transcription-coupled repair (TCR), BER and nucleotide excision repair (NER) to the repair of two non-bulky lesions, 8-oxoguanine (8OG) and uracil (U), in vivo under non-growth conditions. We demonstrate that both TCR and NER are utilized by Escherichia coli to repair 8OG and U. Additionally, the relative level of recognition of these lesions by BER and NER suggests that TCR can utilize components of either pathway for lesion removal, depending upon their availability. These findings indicate a dynamic flexibility of DNA repair pathways in the removal of non-bulky DNA lesions in prokaryotes, and reveal their respective contributions to the repair of 8OG and U in vivo.
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http://dx.doi.org/10.1016/j.dnarep.2010.04.004 | DOI Listing |
J Am Chem Soc
January 2025
Department of Chemistry, Yale University, New Haven, Connecticut 06520, United States.
Ribonucleotide reductase (RNR) is essential for DNA synthesis and repair in all living organisms. The mechanism of RNR requires long-range radical transport through a proton-coupled electron transfer (PCET) pathway spanning two different protein subunits. Herein, the direct PCET reaction between the interfacial tyrosine residues, Y356 and Y731, is investigated with a vibronically nonadiabatic theory that treats the transferring proton and all electrons quantum mechanically.
View Article and Find Full Text PDFColorectal carcinoma (CRC) progression is associated with an increase in PROX1+ tumor cells, which exhibit features of CRC stem cells and contribute to metastasis. Here, we aimed to provide a better understanding to the function of PROX1+ cells in CRC, investigating their progeny and their role in therapy resistance. PROX1+ cells in intestinal adenomas of ApcMin/+ mice expressed intestinal epithelial and CRC stem cell markers, and cells with high PROX1 expression could both self-renew tumor stem/progenitor cells and contribute to differentiated tumor cells.
View Article and Find Full Text PDFBiochem J
January 2025
School of Science, University of Waikato, Hamilton, Waikato, 3216, New Zealand.
DNA-joining by ligase and polymerase enzymes has provided the foundational tools for generating recombinant DNA and enabled the assembly of gene and genome-sized synthetic products. Xenobiotic nucleic acid (XNA) analogues of DNA and RNA with alternatives to the canonical bases, so-called 'unnatural' nucleobase pairs (UBP-XNAs), represent the next frontier of nucleic acid technologies, with applications as novel therapeutics and in engineering semi-synthetic biological organisms. To realise the full potential of UBP-XNAs, researchers require a suite of compatible enzymes for processing nucleic acids on a par with those already available for manipulating canonical DNA.
View Article and Find Full Text PDFACS Chem Neurosci
January 2025
Department of Chemistry, University of Nebraska-Lincoln, Lincoln, Nebraska 68588, United States.
Hibernating mammals such as the thirteen-lined ground squirrel () experience significant reductions in oxidative metabolism and body temperature when entering a state known as torpor. Animals entering or exiting torpor do not experience permanent loss of brain function or other injuries, and the processes that enable such neuroprotection are not well understood. To gain insight into changes in protein function that occur in the dramatically different physiological states of hibernation, we performed quantitative phosphoproteomics experiments on thirteen-lined ground squirrels that are summer-active, winter-torpid, and spring-active.
View Article and Find Full Text PDFCureus
December 2024
Department of Urology, Ehime University Graduate School of Medicine, Toon, JPN.
Background The accurate diagnosis of intraductal carcinoma of the prostate (IDC-P) is occasionally challenging due to the similarity in pathological morphology between IDC-P and high-grade prostatic intraepithelial neoplasia (HGPIN). In this report, we reviewed the pathology of cases previously diagnosed as HGPIN to search for IDC-P cases effectively. In addition, we examined whether those cases had genetic abnormalities.
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