Cellular responses to DNA damage can prevent mutations and death. In this study, we have used high throughput screens and developed a comparative genomic approach, termed Functionome mapping, to discover conserved responses to UVC-damage. Functionome mapping uses gene ontology (GO) information to link proteins with similar biological functions from different organisms, and we have used it to compare 303, 311 and 288 UVC-toxicity modulating proteins from Escherichia coli, Schizosaccharomyces pombe and Saccharomyces cerevisiae, respectively. We have demonstrated that all three organisms use DNA repair, translation and aerobic respiration associated processes to modulate the toxicity of UVC, with these last two categories highlighting the importance of ribosomal proteins and electron transport machinery. Our study has demonstrated that comparative genomic approaches can be used to identify conserved responses to damage, and suggest roles for translational machinery and components of energy metabolism in optimizing the DNA damage response.
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http://dx.doi.org/10.1016/j.ygeno.2010.12.005 | DOI Listing |
Sci Rep
December 2024
Department of Orthopedics, The Second Affiliated hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi Province, China.
The DNA cross-link repair 1B (DCLRE1B) gene is involved in repairing cross-links between DNA strands, including those associated with Hoyeraal-Hreidarsson syndrome and congenital dyskeratosis. However, its role in tumours is not well understood. DCLRE1B expression profiles were examined in tumour tissues and normal tissues using TCGA, GTEx, and TARGET datasets.
View Article and Find Full Text PDFNat 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 PDFNat Commun
December 2024
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, 06511, USA.
Polo-like kinase 1 (PLK1) protects against genome instability by ensuring timely and accurate mitotic cell division, and its activity is tightly regulated throughout the cell cycle. Although the pathways that initially activate PLK1 in G2 are well-characterized, the factors that directly regulate mitotic PLK1 remain poorly understood. Here, we identify that human PLK1 activity is sustained by the DNA damage response kinase Checkpoint kinase 2 (Chk2) in mitosis.
View Article and Find Full Text PDFJ Pediatr Hematol Oncol
January 2025
Medical Faculty, University of Belgrade.
Nijmegen breakage syndrome (NBS) is a rare primary immunodeficiency disease due to a pathogenic variant in the NBN gene causing impaired DNA repair and increased predisposition for lymphoid malignancy. By contrast, solid tumors have been rarely reported. Neuroblastoma (NB) is a rare childhood solid tumor, associated with the worse outcome if MYCN oncogene is amplified.
View Article and Find Full Text PDFFront Pharmacol
December 2024
Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science, Wuhan, China.
Non-small cell lung cancer (NSCLC) constitutes a significant proportion of lung cancer cases, and despite advancements in treatment modalities, radiotherapy resistance remains a substantial hurdle in effective cancer management. Exosomes, which are small vesicles secreted by cells, have emerged as pivotal players in intercellular communication and influence various biological processes, including cancer progression and the response to therapy. This review discusses the intricate role of exosomes in the modulation of NSCLC radiosensitivity.
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