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http://dx.doi.org/10.5352/JLS.2005.15.4.542

Involvement of Brca1 in DNA Interstrand Cross-link Repair Through Homologous Recombination-independent Process  

Yun, Jean-Ho (Medical Research Center for Cancer Molecular Therapy, College of Medicine, Dong-A University, Department of Biochemistry, College of Medicine, Dong-A University)
Publication Information
Journal of Life Science / v.15, no.4, 2005 , pp. 542-547 More about this Journal
Abstract
Hypersensitivity of cells lacking Brcal to DNA interstrand .ross-link (ICL) agents such as cisplatin and mitomycin C(MMC) implicates the important role of Brcal in cellular response following ICL treatment. Brca1 plays an essential role in DNA double-strand break (DSB) repair through homologous recombination (HR)-dependent and -independent process. Recently, our group has been reported that Brca1 involves in cellular ICL response through HR-dependent repair process (Yun J. et at., Oncogene 2005). In this report, the involvement of Brca1 protein in HR-independent repair process is examined using isogenic $p53^{-/-}\;and\;p53^{-/-}\;Brcal^{-/-}$ mouse embryonic fibroblast (MEF) and psoralen cross-linked reporter reactivation assay. Brcal-deficient MEFs showed significantly low HR-independent repair activity compare to Brca1-proficient MEFs. Hypersensitivity to MMC and ICL reporter repair activity were restored by the reconstitution of Brca1 expression. Interestingly, MEFs expressing exon 11-deleted isoform of Brca1 $(Brca1^{\Delta11/\Delta11})$ showed high resistance to MMC and ICL reporter repair activity comparable to Brca1-reconstituted MEFs. Taken together, these results suggest that Brca1 involves in ICL repair through not only HR-dependent process but also HR-independent process using N-terminal RINC finger domain or C-terminal BRCT domain rather than exon 11 region which mediate interaction with Rad50.
Keywords
Brca1; mitomycin C; DNA interstrand cross-link (ICL) repair; Recombinant-independent;
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