Sammendrag
We studied the repair of cyclobutane pyrimidine dimers (CPDs) in the 5' terminal part of the transcriptionally inactive O6-methylguanine-D NA methyltransferase (MGMT) gene of MGMT-deficient human cell lines ( A172, A-253 and WI-38 VA13) and in a proficient cell line (HaCaT), in which the MGMT gene was transcribed. Repair rates in the MGMT gene w ere compared with those in the active uracil-DNA glycosylase (UNG) an d c-myc genes, and those in the repressed X-linked 754 locus and the RNA polymerase I-transcribed ribosomal gene cluster. In the active MG MT gene, there was a distinct strand specificity with more repair in the template (transcribed) strand (TS) than in the non-template stran d (NTS). In contrast, no apparent strand bias in the repair of CPDs w as observed in the inactive MGMT gene in the MGMT deficient cell line s, although the rates of repair varied between different cell lines. Repair in the inactive MGMT gene was consistently lower than repair i n the NTSs of the expressed genes, and approached the generally poor repair of the repressed 754 locus. Whereas repair in the UNG gene was strand-specific in HaCaT, A-172 and WI-38 VA13 cells, no clear stran d bias in repair of this gene was evident in A253 cells and repair wa s relatively inefficient. Although the repair kinetics was essentiall y similar in the two strands of the c-myc gene in all cell lines exam ined, the rate and extent of repair were in general significant, prob ably due to an observed transcription of both strands in the c-myc re gion. In conclusion, our results indicate that the relative rates of repair in inactive MGMT genes are comparable to those of repressed lo ci and are lower than repair rates in the NTSs of active genes, but t he absolute rate of repair varies between different transformed cells .
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