Repair of DNA interstrand cross-links: interactions between homology-dependent and homology-independent pathways.

摘要: DNA interstrand cross-links (ICLs) are complex lesions generated by bifunctional alkylating agents, a class of compounds extensively used in cancer chemotherapy. Formation an ICL covalently links the opposing strands double helix and results severe disruptions normal functions, such as replication, transcription, recombination. Because structural complexity, ICLs most likely recognized variety repair recognition proteins processed through multiple mechanisms. To study involvement different pathways processing, we examined mammalian mutants with distinct deficiencies. We found that presence induces frequent recombination between direct repeat sequences, suggesting single-strand annealing pathway may be important mechanism for removal situated within repeats. Unlike recombination-independent repair, ICL-induced does not require nucleotide excision (NER) mechanism. In cells defective mismatch protein Msh2, level was significantly increased, processing lead to recombinational ICLs. Our suggest involve two error-prone mechanisms depending on sequence context cross-linked site.