Inhibition of excision-repair of ultraviolet damage in human cells by exposure to methyl methanesulfonate.
Unscheduled DNA synthesis and excision of pyrimidine dimers in human cells exposed to ultraviolet let were inhibited by exposure to methyl methanesulfonate (MMS, 1-2 mM), but repair of MMS damage was not inhibited by UV light. Because the pathways for excision of pyrimidine dimers and alkylation damage have previously been shown to be different, this observation implies a direct effect of alkylation on repair enzymes. We estimate that if inhibition is due to protein alkylation, the UV repair system must present an extremely large target to alkylation and may involve a complex of protein subunits in the order of 1 million daltons such that 1 or more alkylations occur per complex at the concentrations used. These results also indicate that the method of exposing cells to 2 DNA-damaging agents to determine whether they are repaired by common or different pathways can be quite unreliable because of other effects on the repair systems themselves.
D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000528:radiation effects; D004260:DNA Repair / Q000187:drug effects*; D004261:DNA Replication / Q000187:drug effects*; D003864:Depression, Chemical; D005260:Female; D005347:Fibroblasts / Q000528:radiation effects; D006801:Humans; D008741:Methyl Methanesulfonate / Q000494:pharmacology*; D010053:Ovary; D014466:Ultraviolet Rays; D014983:Xeroderma Pigmentosum
D004247:DNA; D008741:Methyl Methanesulfonate