The LNA dinucleotide mimic of TpT whose two-sugar puckers are locked in the C3'-endo conformation selectively produces the corresponding cyclobutane pyrimidine dimer under 254 nm irradiation. In the natural series (TpT) the sugar puckers are in a major C2'-endo sugar conformation and the (6-4) photoproduct is also produced. Consequently, this study demonstrates that the C2'-endo conformation of the sugar pucker is necessary for (6-4) photoproduct formation.
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http://dx.doi.org/10.1021/ja077095q | DOI Listing |
Proc Natl Acad Sci U S A
December 2024
Center for Ultrafast Science and Technology, School of Chemistry and Chemical Engineering, School of Physics and Astronomy, Zhang Jiang Institute for Advanced Study, Shanghai Jiao Tong University, Shanghai 200240, China.
Photolyase and cryptochrome belong to a group of structurally similar flavoproteins but with two distinct functions of DNA repair as a photoenzyme and signal transduction as a photoreceptor, respectively, under blue-light illumination. Here, we studied a recently discovered bifunctional cryptochrome (CraCRY) with focus on its repair of UV-induced pyrimidine-pyrimidone (6-4) photoproduct (6-4PP). We used femtosecond spectroscopy and site-directed mutagenesis to map out the critical elementary steps by following the dynamics of initial reactants, various intermediates, and final products.
View Article and Find Full Text PDFCell Death Dis
November 2024
Univ. Grenoble Alpes, CEA, Inserm, IRIG, UA13 BGE, Biomics, Grenoble, France.
Xeroderma Pigmentosum C is a dermal hereditary disease caused by a mutation in the DNA damage recognition protein XPC that belongs to the Nucleotide excision repair pathway. XPC patients display heightened sensitivity to light and an inability to mend DNA damage caused by UV radiation, resulting in the accumulation of lesions that can transform into mutations and eventually lead to cancer. To address this issue, we conducted a screening of siRNAs targeting human kinases, given their involvement in various DNA repair pathways, aiming to restore normal cellular behavior.
View Article and Find Full Text PDFJ Photochem Photobiol B
December 2024
School of Biological Sciences, Indian Association for the Cultivation of Science, Kolkata, West Bengal, India. Electronic address:
Exposure to ultraviolet radiation, which leads to the formation of mutagenic and cytotoxic DNA lesions such as cyclobutane pyrimidine dimers (CPDs) and 6-4 photoproducts (6-4 PPs), can be potentially fatal. The way UVA forms DNA lesions and alters DNA topology and mechanics is still unclear, unlike the cases of UVC and UVB. Herein, Atomic Force Microscopy (AFM) and AFM-based Force Spectroscopy (AFS) have been employed to investigate the topological and mechanical properties of single DNA molecules, bare or E.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
October 2024
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7260.
DNA repair processes modulate genotoxicity, mutagenesis, and adaption. Nucleotide excision repair removes bulky DNA damage, and in , basal excision repair, carried out by UvrA, B, C, and D, with DNA PolI and DNA ligase, occurs genome-wide. In transcription-coupled repair (TCR), the Mfd protein targets template strand (TS) lesions that block RNA polymerase for accelerated repair by the basal repair enzymes.
View Article and Find Full Text PDFCytotechnology
December 2024
Department of Anatomy and Structural Biology, Graduate School of Medicine, University of Yamanashi, 1110 Shimokato, Chuo, 409-3998 Yamanashi Japan.
Unlabelled: In this study, we investigated the effects of blue light and 5-aminolevulinic acid (5-ALA) co-treatment on B16F1 melanoma cells and HaCaT keratinocytes. We focused on cellular responses, including mitochondrial function, DNA integrity, and gene expression. Co-treatment significantly damaged the mitochondria, altered their morphology, induced mitochondrial membrane depolarization, increased intracellular reactive oxygen species, and led to cardiolipin peroxidation in both cell types.
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