Physical Sciences and Mathematics Commons^™

Effects Of The Anticancer Agent Cloretazine On Human Apurinic Endonuclease-1 Activity, Jennifer L. Bushee

Honors Theses

The carbamolyating activity of Cloretazine, a novel anticancer prodrug, modifies protein function and acts synergistically with the choroethyalting species, which a1kylales DNA. The reactive subspecies responsible for carbamolylating activity is methyl isocyanate, which reacts with sulfhydryl groups and amines. DNA repair enzymes have been identified as potential targets for the modification by methyl isocyanate; in particular, base excision repair enzymes. Enzymes in DNA base excision repair include DNA polymerase beta (Pol ?) and apurinic/apyrimidic endonucease-l (APE/Ref-1). APE/Ref-1 hydrolyzes the 5' -phosphodiester DNA backbone from an abasic DNA template, where the base was excised by a DNA glycosylase. The entire nucleotide …