ANTHRAMYCIN--PHYSIOLOGY OF PRODUCTION

目标：这项研究是对先前工作的延续 阐明炭霉素和相关药物与DNA和DNA反应的方式 这些反应的生物学后果。我们的总体目标是 下一阶段是：1)精确描述DNA和染色质的损伤 2)探索和鉴定其生物学特性。 使用人类细胞系和复制的SV-40 DNA的这种损伤的后果 合成，以及3)研究生产和抗性的遗传学 由生产有机体产生的炭霉素。 方法：将使用~1H-核磁共振技术和人工合成技术来探测炭霉素对DNA的损伤 多脱氧核苷酸，并通过生化技术在染色质水平上进行检测。 生物学后果(DNA修复参数、双链断裂、抑制 将在人类细胞系(正常、XP、AT和FA)和 在允许的SV-40复制系统中。质粒和染色体DNA将是 从产生炭霉素的有机体中检测出来。

OBJECTIVES: 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.