The nucleotide-excision repair (NER) system removes bulky DNA adducts
and is thought to be involved in resistance to chemotherapeutic drugs,
which act by damaging DNA. In this study, we have investigated the ab
ility of the NER system to recognize and excise melphalan monoadducts
from a 140-mer DNA substrate. We show that rodent and human cell-free
extracts (CFEs) excise 26-29-nt-long oligomers from a synthetic 140-me
r containing centrally located melphalan adducts. CFEs from cell lines
with mutations in xeroderma pigmentosum group F or G genes did not ex
cise these alkylated oligomers; however, mixing the two CFEs restored
excision activity to the level found with wild-type CFEs. These result
s demonstrate the ability of the NER system to excise melphalan monoad
ducts, and are consistent,vith the hypothesis that NER may be involved
in resistance to melphalan chemotherapy.