Ontology highlight
ABSTRACT:
PROVIDER: PRJEB44262 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Colibactin is a secondary metabolite produced by bacteria present in the human gut and is implicated in the progression of colorectal cancer and inflammatory bowel disease. This genotoxin alkylates deoxyadenosines on opposite strands of host cell DNA to produce DNA interstrand cross-links (ICLs) that block DNA replication. While cells have evolved multiple mechanisms to resolve (“unhook”) ICLs encountered by the replication machinery, little is known about which of these pathways promote resistance to colibactin-induced ICLs. Here, we use Xenopus egg extracts to investigate replication-coupled repair of plasmids engineered to contain site-specific colibactin-ICLs. We show that replication fork stalling at a colibactin-ICL leads to replisome disassembly and activation of the Fanconi anemia ICL repair pathway, which unhooks the colibactin-ICL through nucleolytic incisions. These incisions generate a DNA double-strand break intermediate in one sister chromatid, which can be repaired by homologous recombination, and a monoadduct (“ICL remnant”) in the other. Our data indicate that translesion synthesis past the colibactin-ICL remnant depends on Pol-ita and the Pol-kappa-REV1-Pol-Zitapolymerase complex. Although translesion synthesis past colibactin-induced DNA damage is frequently error-free, it can introduce T>N point mutations that partially recapitulate the mutation signature associated with colibactin exposure in vivo. Taken together, our work provides a molecular framework for understanding how cells tolerate a naturally occurring and clinically relevant ICL.
2025-09-11 | PXD055646 | Pride
Project description:Primordial germ cell DNA demethylation and development require DNA translesion synthesis
| PRJNA1068075 | ENA
Project description:The NuA4 complex promotes Translesion Synthesis (TLS) - mediated DNA damage tolerance
| PRJNA276018 | ENA
Project description:Benzo[a]pyrene (BaP), a polycyclic aromatic hydrocarbon, is the major cause of lung cancer. It forms covalent DNA adducts after metabolic activation and induces mutations. We have developed a method capturing oligonucleotides carrying bulky base adducts, including UV-induced cyclobutane pyrimidine dimers (CPDs) and BaP diol epoxide-deoxyguanosine (BPDE-dG), which are removed from the genome by nucleotide excision repair. The isolated oligonucleotides are ligated to adaptors and after damage-specific immunoprecipitation the adaptor-ligated oligonucleotides are converted to dsDNA with an appropriate translesion DNA synthesis (TLS) polymerase followed by PCR amplification and next-generation sequencing (NGS) to generate genome-wide repair maps. We have named this method as translesion eXcision Repair-sequencing (tXR-seq). In contrast to our previously described XR-seq method, the tXR-seq does not depend on repair/removal of the damage in the excised oligonucleotides and hence it is applicable to essentially all DNA damages processed by nucleotide excision repair. Here, we present the excision repair maps for CPDs and BPDE-dG adducts generated by tXR-Seq for the human genome. Additionally, we observe novel sequence specificity of BPDE-dG excision repair by using tXR-seq.
2017-06-12 | GSE97675 | GEO
Project description:Biallelic mutations in the SPRTN gene cause an autosomal recessive progeroid disease known as Ruijs–Aalfs syndrome. Patients with Ruijs–Aalfs syndrome display symptoms of premature ageing and typically develop hepatocellular carcinoma during adolescence. To study the functional role of this protein, we generated knock-in mice (Sprtn Y118C/Y118C) that largely recapitulate the Ruijs–Aalfs phenotype. These mice harbour the equivalent of the Y117C missense mutation described in Ruijs–Aalfs patients. SPRTN has recently been implicated in DNA repair, specifically in the resolution of DNA–protein crosslinks (DPCs), which facilitates replisome bypass and allows translesion synthesis across DPC adducts. Understanding this DNA repair pathway is of paramount importance, as cells lacking SPRTN are not viable, and DNA–protein lesions can be induced by UV light, ionizing radiation, or normal cellular metabolism. Moreover, a broad spectrum of chemotherapeutic drugs induces protein–DNA crosslinking. In our study, we compared the bulk transcriptome of Sprtn Y118C/Y118C and wild-type mice using RNA extracted from liver tissue.
2025-09-27 | GSE268005 | GEO
Project description:Translesion DNA synthesis-driven mutagenesis in very early embryogenesis of fast cleaving embryos
| PRJNA677917 | ENA
Project description:Antimicrobial-induced DNA damage, and subsequent repair via upregulation of DNA repair factors, including error-prone translesion polymerases, can lead to the increased accumulation of mutations in the microbial genome, and ultimately increased risk of acquired mutations associated with antimicrobial resistance. While this phenotype is well described in bacterial species, it is less thoroughly investigated amongst microbial fungi. Here, we monitor DNA damage induced by antifungal agents in the fungal pathogen Candida albicans, and find that commonly used antifungal drugs are able to induce DNA damage, leading to the upregulation of transcripts encoding predicted error-prone polymerases and related factors. We focus on REV1, encoding a putative error-prone polymerase, and find that while deleting this gene in C. albicans leads to increased sensitivity to DNA damage, it also unexpectedly renders cells more likely to incur mutations and evolve resistance to antifungal agents. We further find that deletion of REV1 leads to a significant depletion in the uncharacterized protein Shm1, which itself plays a role in fungal mutagenesis. Together, this work lends new insight into previously uncharacterized factors with important roles in the DNA damage response, mutagenesis, and the evolution of antifungal drug resistance.
2025-05-07 | PXD055008 | Pride