Genome maintenance is orchestrated by a highly regulated DNA damage response with specific DNA repair pathways. Here, we investigate the phylogenetic diversity in the recognition and repair of three well-established DNA lesions, primarily repaired by base excision repair (BER) and ribonucleotide excision repair (RER): (1) 8-oxoguanine, (2) abasic site, and (3) incorporated ribonucleotide in DNA in 11 species: and Using quantitative mass spectrometry, we identified 337 binding proteins across these species. Of these proteins, 99 were previously characterized to be involved in DNA repair. Through orthology, network, and domain analysis, we linked 44 previously unconnected proteins to DNA repair. Our study presents a resource for future study of the crosstalk and evolutionary conservation of DNA damage repair across all domains of life.
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http://dx.doi.org/10.1016/j.isci.2023.106778 | DOI Listing |
J Cell Sci
January 2025
Department of Biomedical Engineering, Northwestern University, Evanston, Illinois, 60208, USA.
Disrupted nuclear shape is associated with multiple pathological processes including premature aging disorders, cancer-relevant chromosomal rearrangements, and DNA damage. Nuclear blebs (i.e.
View Article and Find Full Text PDFiScience
February 2025
Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Xuzhou Medical University, Xuzhou, Jiangsu, China.
Pattern recognition receptors (PRRs), consisting of Toll-like receptors, RIG-I-like receptors, cytosolic DNA sensors, and NOD-like receptors, sense exogenous pathogenic molecules and endogenous damage signals to maintain physiological homeostasis. Upon activation, PRRs stimulate the sensitization of nuclear factor κB, mitogen-activated protein kinase, TANK-binding kinase 1-interferon (IFN) regulatory factor, and inflammasome signaling pathways to produce inflammatory factors and IFNs to activate Janus kinase/signal transducer and activator of transcription signaling pathways, resulting in anti-infection, antitumor, and other specific immune responses. Palmitoylation is a crucial type of post-translational modification that reversibly alters the localization, stability, and biological activity of target molecules.
View Article and Find Full Text PDFBJUI Compass
January 2025
Division of Medical Oncology A Policlinico Umberto I Rome Italy.
Background: We present a systematic review and meta-analysis of randomized clinical trials (RCTs) with PARPi either as monotherapy or in combination with an androgen receptor-targeted agent (ARTA) in first- and second-line settings.
Methods: Primary endpoints are radiographic progression free survival (rPFS) and overall survival (OS) in patients with mCRPC and either unselected, homologous recombination repair wild-type (HRR-), homologous recombination repair mutated (HRR+) or with BRCA1, BRCA2, or ATM mutation. The effect of PARPi + ARTA in the second-line setting is also explored.
Unlabelled: Transparent and accurate reporting in early phase dose-finding (EPDF) clinical trials is crucial for informing subsequent larger trials. The SPIRIT statement, designed for trial protocol content, does not adequately cover the distinctive features of EPDF trials. Recent findings indicate that the protocol contents in past EPDF trials frequently lacked completeness and clarity.
View Article and Find Full Text PDFUnlabelled: Early phase dose-finding (EPDF) trials are key in the development of novel therapies, with their findings directly informing subsequent clinical development phases and providing valuable insights for reverse translation. Comprehensive and transparent reporting of these studies is critical for their accurate and critical interpretation, which may improve and expedite therapeutic development. However, quality of reporting of design characteristics and results from EPDF trials is often variable and incomplete.
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