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  • 1
    Publication Date: 1998-08-14
    Description: The breast and ovarian cancer susceptibility gene BRCA1 encodes a zinc finger protein of unknown function. Association of the BRCA1 protein with the DNA repair protein Rad51 and changes in the phosphorylation and cellular localization of the protein after exposure to DNA-damaging agents are consistent with a role for BRCA1 in DNA repair. Here, it is shown that mouse embryonic stem cells deficient in BRCA1 are defective in the ability to carry out transcription-coupled repair of oxidative DNA damage, and are hypersensitive to ionizing radiation and hydrogen peroxide. These results suggest that BRCA1 participates, directly or indirectly, in transcription-coupled repair of oxidative DNA damage.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gowen, L C -- Avrutskaya, A V -- Latour, A M -- Koller, B H -- Leadon, S A -- CA40453/CA/NCI NIH HHS/ -- CA70490/CA/NCI NIH HHS/ -- IP50CA58223/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1998 Aug 14;281(5379):1009-12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Curriculum in Genetics and Molecular Biology and Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9703501" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; BRCA1 Protein/genetics/*physiology ; Cell Line ; DNA Damage ; *DNA Repair ; Hydrogen Peroxide ; Mice ; Oxidation-Reduction ; Stem Cells ; Thymine/analogs & derivatives/immunology/metabolism ; Transcription, Genetic ; Ultraviolet Rays
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2003-06-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gowen, Lori C -- Avrutskaya, Anna V -- Latour, Anne M -- Koller, Beverly H -- Leadon, Steven A -- New York, N.Y. -- Science. 2003 Jun 13;300(5626):1657.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12805518" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
    ISSN: 1573-904X
    Keywords: oligonucleotide ; endocytosis ; delivery ; surfactant
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. A factor limiting the effectiveness of antisense (AS) deoxyoligonucleotides (ODNs) is inefficient transport to their sites of action in the cytoplasm and in the nucleus. The extent of ODN transfer from endosomes to cytosol seems to be an important determinant of ODN effects. Consequently, the development of compounds (adjuvants) that enhance endosome to cytosol transfer may be vital in AS ODN therapeutics. Methods. In this report, we evaluated compounds for their potential to enhance the effects of phosphorothioate ODNs. The test system used a CHO cell line expressing the enzyme chloramphenicol acetyl-transferase (CAT) under the control of an inducible promoter. Several potential endosomal disrupting adjuvants were screened, including: (a) fusogenic peptides; (b) a pH sensitive polymer; (c) polymeric dendrimers, (d) cationic liposomes and (e) a pH sensitive surfactant N-dodecyl 2-imidazole-propionate (DIP). ODN effects were evaluated at the protein level by quantitating levels of CAT. Results. The use of AS ODN in co-incubation with the GALA peptide, cationic liposomes or 5th generation dendrimers resulted in a 35–40% reduction in CAT expression. The mis-matched ODN had no effect on CAT expression. Only modest effects were observed with the other adjuvants. DIP did not increase ODN activity by itself; however, when the liposomal form was used a significant reduction (48%) in CAT activity was seen. Conclusions. We found the fusogenic peptide GALA, dendrimers, as well as the liposomal form of DIP, could significantly enhance the effects of ODNs.
    Type of Medium: Electronic Resource
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