This research is a continuation of previous work carried out to elucidate the manner in which anthramycin and related drugs react with DNA and the biological consequences of these reactions. Our broad objectives during the next period are: 1) to precisely characterize t damage to DNA and chromatin caused by anthramycin, 2) to explore and characterize the biological consequences of this damage using human cell lines and replicative SV-40 DNA synthesis, and 3) to examine the genetics of production and resistance to anthramycin by the producing organism. APPROACH: DNA damage by anthramycin will be probed using 1H-NMR with synthetic polydeoxynucleotides, and at the chromatin level by biochemical techniques. Biological consequences (DNA repair parameters, double strand breaks, inhibition of replication) will be followed in human cell lines (normal, XP, AT and FA) and in a permissive SV-40 replication system. Plasmid and chromosomal DNA will be examined from the anthramycin producing organism.
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