Previous work with the classic T4 endonuclease V digestion of DNA from irradiated cells followed by Southern hybridization led to the conclusion that lacks transcription-coupled repair (TCR). This conclusion was reinforced by the Genome Project, which revealed that lacks Cockayne syndrome WD repeat protein (CSA), CSB, or UV-stimulated scaffold protein A (UVSSA) homologs, whose orthologs are present in eukaryotes ranging from to humans that carry out TCR. A recently developed excision assay and the excision repair-sequencing (XR-Seq) method have enabled genome-wide analysis of nucleotide excision repair in various organisms at single-nucleotide resolution and in a strand-specific manner. Using these methods, we have discovered that S2 cells carry out robust TCR comparable with that observed in mammalian cells. Our findings provide critical new insights into the mechanisms of TCR among various different species.
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http://dx.doi.org/10.1074/jbc.AC119.011448 | DOI Listing |
Nat Commun
December 2024
Division of Protein & Nucleic Acid Chemistry, MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK.
The rate and pattern of mutagenesis in cancer genomes is significantly influenced by DNA accessibility and active biological processes. Here we show that efficient sites of replication initiation drive and modulate specific mutational processes in cancer. Sites of replication initiation impede nucleotide excision repair in melanoma and are off-targets for activation-induced deaminase (AICDA) activity in lymphomas.
View Article and Find Full Text PDFOncol Res
December 2024
Clinical Oncology Unit, Careggi University Hospital, Florence, 50134, Italy.
Background: Platinum chemotherapy (CT) remains the backbone of systemic therapy for patients with small-cell lung cancer (SCLC). The nucleotide excision repair (NER) pathway plays a central role in the repair of the DNA damage exerted by platinum agents. Alteration in this repair mechanism may affect patients' survival.
View Article and Find Full Text PDFCureus
November 2024
Department of Cardiothoracic Surgery, Castle Hill Hospital, Cottingham, GBR.
This case report describes a rare instance of massive right ventricular myxoma (RVM). A 36-year-old woman initially presented with progressive breathlessness and chest heaviness. Imaging revealed a large mass in the mediastinum, which was initially thought to be a pericardial cyst, and it was unclear whether the mass was intracardiac or extracardiac.
View Article and Find Full Text PDFAsian Pac J Cancer Prev
December 2024
Department of Oncology, Krishna Vishwa Vidyapeeth "Deemed to be University", Taluka-Karad, Dist- Satara, Pin-415 539, (Maharashtra) India.
Background: Systemic chemotherapy constitutes an indispensable component of breast cancer (BC) management, where therapeutic drug combinations such as anthracyclines, platinum compounds, and taxanes form the cornerstone of standard treatment protocols. Although DNA repair genes are pivotal in cancer susceptibility, their specific roles in mediating acute or chronic toxicity outcomes induced by chemotherapy remain undetermined. Consequently, this study was planned to elucidate the impact of polymorphisms in base excision repair (BER) genes, including XRCC1, XRCC2, XRCC3, APE1, and hOGG1, on treatment response and toxicity outcomes in BC patients undergoing paclitaxel and doxorubicin-based chemotherapy within an Indian population.
View Article and Find Full Text PDFSci Rep
December 2024
Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN, 55455, USA.
Exposure to reactive oxygen species (ROS) can induce DNA-protein crosslinks (DPCs), unusually bulky DNA lesions that block replication and transcription and play a role in aging, cancer, cardiovascular disease, and neurodegenerative disorders. Repair of DPCs depends on the coordinated efforts of proteases and DNA repair enzymes to cleave the protein component of the lesion to smaller DNA-peptide crosslinks which can be processed by tyrosyl-DNA phosphodiesterases 1 and 2, nucleotide excision and homologous recombination repair pathways. DNA-dependent metalloprotease SPRTN plays a role in DPC repair, and SPRTN-deficient mice exhibit an accelerated aging phenotype and develop liver cancer early in life.
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