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Repair of Mitomycin-C Induced DNA Interstrand Cross-Link in Mammalian Cells
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Abstract:
Objective:To study the repair mechanisms of ICLs in mammalian cells. Methods: A site-specific MMC cross-link was placed between the promoter and the coding region to inactivate the expression of luciferase genes from reporter plasmids. An in vivo reactivation assay was developed to examine the removal of ICLs in cultured cells. Results: MMC cross-link was removed in repair-proficient cells in the absence of undamaged homologous sequences, suggesting the existence of an ICL repair pathway that is independent of homologous recombination. Mutant cell lines deficient in the NER pathway were examined and found to be highly defective in the recombination independent repair of ICLs, while mutants deficient in homologous recombination were found to be proficient. Mutation analysis of plasmids recovered from transfected cells showed frequent base substitutions at or near the positions of MMC crosslinks. Conclusion: Recombination-independent ICL pathway exists in mammalian cells and NER involve in the repair with an error-prone mechanism.
Keywords:
interstrand crosslink ; mitomycin-C ; nucleotide excision repair
