ANTHRAMYCIN--PHYSIOLOGY OF PRODUCTION

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.