Lack of correlation between degree of interference with transcription and rate of strand specific repair in the HPRT gene of diploid human fibroblasts.
The model that transcription-coupled excision repair reflects the interference of DNA damage with the transcription process predicts that the rate of such excision repair will be related to the degree to which a particular type of lesion blocks transcription. We tested this by measuring the rate of excision repair of guanine adducts formed in the HPRT gene of diploid human fibroblasts and in the overall genome by two structurally related polycyclic carcinogens, 1-nitrosopyrene (1-NOP) and N-acetoxy-2-acetylaminofluorene (N-AcO-AAF) and comparing the results with those we found previously using benzo[a]pyrene diol epoxide (BPDE). We also measured the degree of interference with in vitro transcription by these adducts. Our results showed that, although BPDE adducts are four times more effective than 1-NOP adducts in blocking transcription, the preferential and strand-specific repair of 1-NOP adducts was twice as fast as that of BPDE adducts. Excision repair of N-AcO-AAF adducts was significantly slower than that of BPDE adducts and was not strand-specific. The efficiency of blocking of transcription by deacetylated N-AcO-AAF adducts was similar to 1-NOP adducts. Therefore, the extent to which a particular lesion blocks transcription in vitro does not predict its rate of preferential or transcription-coupled excision repair.
McGregor
W G
WG
Department of Microbiology, Cancer Center, Michigan State University, East Lansing 48824-1316, USA.
Mah
M C
MC
Chen
R W
RW
Maher
V M
VM
McCormick
J J
JJ
D000099:Acetoxyacetylaminofluorene / Q000633:toxicity; D002273:Carcinogens / Q000633:toxicity; D002478:Cells, Cultured; D018736:DNA Adducts / Q000737:chemistry / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics*; D004261:DNA Replication / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D007700:Kinetics; D008957:Models, Genetic; D011721:Pyrenes / Q000633:toxicity; D012313:RNA / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects
D002273:Carcinogens; D018736:DNA Adducts; D011721:Pyrenes; D000099:Acetoxyacetylaminofluorene; D012313:RNA; C044707:1-nitrosopyrene; D007041:Hypoxanthine Phosphoribosyltransferase