Search results for " Repair"
showing 10 items of 721 documents
Deinococcus radiodurans' SRA-HNH domain containing protein Shp (Dr1533) is involved in faithful genome inheritance maintenance following DNA damage
2018
WOS:000452343100012; International audience; Background: Deinococcus radiodurans R1 (DR) survives conditions of extreme desiccation, irradiation and exposure to genotoxic chemicals, due to efficient DNA breaks repair, also through Mn2+ protection of DNA repair enzymes. Methods: Possible annotated domains of the DR1533 locus protein (Shp) were searched by bioinformatic analysis. The gene was cloned and expressed as fusion protein. Band-shift assays of Shp or the SRA and HNH domains were performed on oligonucleotides, genomic DNA from E. coif and DR. slip knock-out mutant was generated by homologous recombination with a kanamycin resistance cassette. Results: DR1533 contains an N-terminal SRA…
Molecular modes of action of cantharidin in tumor cells
2005
Cancer chemotherapy is often limited by patient's toxicity and tumor drug resistance indicating that new drug development and modification of existing drugs is critical for improving the therapeutic response. Traditional Chinese medicine is a rich source of potential anticancer agents. In particular, cantharidin (CAN), the active principle ingredient from the blister beetle, Mylabris, has anti-tumor activity, but the cytotoxic mechanism is unknown. In leukemia cells, cantharidin induces apoptosis by a p53-dependent mechanism. Cantharidin causes both DNA single- and double-strand breaks. Colony-forming assays with knockout and transfectant cells lines showed that DNA polymerase beta, but not…
Poly(ADP-ribosyl)ation accelerates DNA repair in a pathway dependent on Cockayne syndrome B protein
2003
Activation of poly(ADP-ribose)polymerases 1 and 2 (PARP-1 and PARP-2) is one of the earliest responses of mammalian cells to DNA damage by numerous genotoxic agents. We have analysed the influence of PARP inhibition, either achieved by over-expression of the DNA binding domain of PARP-1 or by treatment with 3,4-dihydro-5-[4-(1-piperidinyl)butoxyl]-1(2H)-isoquinolinone, on the repair of single-strand breaks (SSB), pyrimidine dimers and oxidative base modifications sensitive to Fpg protein (mostly 8-hydroxyguanine) in mammalian cells at very low, non-cytotoxic levels of DNA damage. The data show that the repair rates of all three types of DNA damage are significantly lower in PARP-inhibited c…
Parvovirus B19 nonstructural protein-induced damage of cellular DNA and resultant apoptosis.
2010
Parvovirus B19 is a widespread virus with diverse clinical presentations. The viral nonstructural protein, NS1, binds to and cleaves the viral genome, and induces apoptosis when transfected into nonpermissive cells, such as hepatocytes. We hypothesized that the cytotoxicity of NS1 in such cells results from chromosomal DNA damage caused by the DNA-nicking and DNA-attaching activities of NS1. Upon testing this hypothesis, we found that NS1 covalently binds to cellular DNA and is modified by PARP, an enzyme involved in repairing single-stranded DNA nicks. We furthermore discovered that the DNA nick repair pathway initiated by poly(ADPribose)polymerase and the DNA repair pathways initiated by …
Role of glutathione in cell nucleus
2010
Cells with high proliferation rate have high glutathione levels. This typical feature of cancer cells is viewed usually as a defence mechanism against ionizing radiation or chemotherapy. Efforts have been made in order to decrease cellular glutathione levels in tumours as a necessary pre-treatment for cancer therapy. However, very few reports have considered cellular glutathione as a physiological tool for cells to proliferate and that most of this high glutathione levels were located in the nucleus. The role of nuclear glutathione in cell physiology has become more important in the last years. This review summarizes new findings that point to the nuclear reduced status as an environment th…
Interaction with OGG1 Is Required for Efficient Recruitment of XRCC1 to Base Excision Repair and Maintenance of Genetic Stability after Exposure to O…
2015
International audience; XRCC1 is an essential protein required for the maintenance of genomic stability through its implication in DNA repair. The main function of XRCC1 is associated with its role in the single-strand break (SSB) and base excision repair (BER) pathways that share several enzymatic steps. We show here that the polymorphic XRCC1 variant R194W presents a defect in its interaction with the DNA glycosylase OGG1 after oxidative stress. While proficient for single-strand break repair (SSBR), this variant does not colocalize with OGG1, reflecting a defect in its involvement in BER. Consistent with a role of XRCC1 in the coordination of the BER pathway, induction of oxidative base …
Circadian rhythms and chemical carcinogenesis: Potential link. An overview.
2009
Circadian rhythm is an integral and not replaceable part of the organism's homeostasis. Its signalling is multidimensional, overlooking global networks such as chromatin remodelling, cell cycle, DNA damage and repair as well as nuclear receptors function. Understanding its global networking will allow us to follow up not only organism dysfunction and pathology (including chemical carcinogenesis) but well-being in general having in mind that time is not always on our side. The authors thank ECNIS (Environmental Cancer, Nutrition and Individual Susceptibility), a network of excellence operating within the European Union 6th Framework Program, Priority 5: Food Quality and Safety (Contract no. …
DNA Junction Ligands Trigger DNA Damage and Are Synthetic Lethal with DNA Repair Inhibitors in Cancer Cells.
2019
International audience; Translocation of DNA and RNA polymerases along their duplex substrates results in DNA supercoiling. This torsional stress promotes the formation of plectonemic structures, including three-way DNA junction (TWJ), which can block DNA transactions and lead to DNA damage. While cells have evolved multiple mechanisms to prevent the accumulation of such structures, stabilizing TWJ through ad hoc ligands offer an opportunity to trigger DNA damage in cells with high level of transcription and replication, such as cancer cells. Here, we develop a series of azacryptand-based TWJ ligands, we thoroughly characterize their TWJ-interacting properties in vitro and demonstrate their…
APE/Ref-1 and the mammalian response to genotoxic stress.
2003
Human apurinic/apyrimidinic endonuclease/redox factor-1 (hAPE/Ref-1) is a multifunctional protein involved in the repair of DNA damaged by oxidative or alkylating compounds as well as in the regulation of stress inducible transcription factors such as AP-1, NF-kappaB, HIF-1 and p53. With respect to transcriptional regulation, both redox dependent and independent mechanisms have been described. APE/Ref-1 also acts as a transcriptional repressor. Recent data indicate that APE/Ref-1 negatively regulates the activity of the Ras-related GTPase Rac1. How these different physiological activities of APE/Ref-1 are coordinated is poorly understood. So far, convincing evidence is available that the ex…
Molecular and functional analysis of the (6-4) photolyase from the hexactinellid Aphrocallistes vastus.
2003
The hexactinellid sponges (phylum Porifera) represent the phylogenetically oldest metazoans that evolved 570-750 million years ago. At this period exposure to ultraviolet (UV) light exceeded that of today and it may be assumed that this old taxon has developed a specific protection system against UV-caused DNA damage. A cDNA was isolated from the hexactinellid Aphrocallistes vastus which comprises high sequence similarity to genes encoding the protostomian and deuterostomian (6-4) photolyases. Subsequently functional studies were performed. It could be shown that the sponge gene, after transfection into mutated Escherichia coli, causes resistance of the bacteria against UV light. Recombinan…