Document Detail

Repair of cyclobutane pyrimidine dimers in the O6-methylguanine-DNA methyltransferase (MGMT) gene of MGMT proficient and deficient human cell lines and comparison with the repair of other genes and a repressed X-chromosomal locus.
MedLine Citation:
PMID:  9653449     Owner:  NLM     Status:  MEDLINE    
We studied the repair of cyclobutane pyrimidine dimers (CPDs) in the 5' terminal part of the transcriptionally inactive O6-methylguanine-DNA 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 were compared with those in the active uracil-DNA glycosylase (UNG) and c-myc genes, and those in the repressed X-linked 754 locus and the RNA polymerase I-transcribed ribosomal gene cluster. In the active MGMT gene, there was a distinct strand specificity with more repair in the template (transcribed) strand (TS) than in the non-template strand (NTS). In contrast, no apparent strand bias in the repair of CPDs was observed in the inactive MGMT gene in the MGMT deficient cell lines, although the rates of repair varied between different cell lines. Repair in the inactive MGMT gene was consistently lower than repair in 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 strand bias in repair of this gene was evident in A253 cells and repair was relatively inefficient. Although the repair kinetics was essentially similar in the two strands of the c-myc gene in all cell lines examined, the rate and extent of repair were in general significant, probably due to an observed transcription of both strands in the c-myc region. In conclusion, our results indicate that the relative rates of repair in inactive MGMT genes are comparable to those of repressed loci and are lower than repair rates in the NTSs of active genes, but the absolute rate of repair varies between different transformed cells.
F Skorpen; C Skjelbred; B Alm; P A Aas; S A Schønberg; H E Krokan
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Mutation research     Volume:  407     ISSN:  0027-5107     ISO Abbreviation:  Mutat. Res.     Publication Date:  1998 Jun 
Date Detail:
Created Date:  1998-07-21     Completed Date:  1998-07-21     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0400763     Medline TA:  Mutat Res     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  227-41     Citation Subset:  IM    
UNIGEN Center for Molecular Biology, Norwegian University of Science and Technology, Trondheim, Norway.
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MeSH Terms
Cell Line
DNA Repair*
O(6)-Methylguanine-DNA Methyltransferase / genetics*
Pyrimidine Dimers / genetics*
X Chromosome / genetics*
Reg. No./Substance:
0/Pyrimidine Dimers; EC Methyltransferase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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