DNA repair capacity: Inconsistency between effect of over-expression of five NER genes and the correlation to mRNA levels in primary lymphocytes

Research output: Contribution to journalJournal article – Annual report year: 2000Researchpeer-review

Without internal affiliation

  • Author: Vogel, Ulla

    National Research Centre for the Working Environment

  • Author: Dybdahl, Marianne

    National Research Centre for the Working Environment

  • Author: Frentz, Gerda

    University of Copenhagen

  • Author: Nexø, Bjørn A.

    National Research Centre for the Working Environment

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We have previously shown that high DNA repair capacity protects psoriasis patients against chemically induced basal cell carcinoma [Dybdahl et al. Mutat. Res. 433 (1999) 15-22]. We have used the same study persons to investigate the correlation between expression of eight genes involved in nucleotide excision repair and DNA repair capacity. mRNA levels of XPA, XPB, XPC, XPD, XPF, XPG, CSB and ERCC1 in primary lymphocytes from 33 individuals were quantified by dot-blots and normalized to β-actin. ERCC1 and XPD mRNA quantities were highly correlated (r = 0.89; P < 10-11) while XPA, XPB, XPC, XPG, XPFand CSB mRNAs were moderately correlated (r = 0.2-0.7). Thus, the mRNA expressions seem to fall in at least two groups. There was a three to sevenfold variation in the expression levels of the mRNAs. This is in contrast to the more than a hundredfold variation in mRNA levels reported in cancer patients. DNA repair capacity was measured in a host cell reactivation assay, where primary lymphocytes were transfected with an UV-irradiated plasmid encoding firefly-luciferase. Only ERCC1 and XPD mRNA levels correlated with the DNA repair capacity (P < 0.03). In order to see if ERCC1 or XPD activity was limiting for DNA repair, we cotransfected with plasmids encoding NER genes, thus over-expressing either XPB, XPC, XPD, CSB or ERCC1 in the host cell reactivation assay. Only XPB over-expression increased DNA repair capacity. Thus, there is no indication that neither XPD nor ERCC1 limits the DNA repair capacity. However, our results indicate that ERCC1 and XPD mRNA levels may be used as a proxy for DNA repair capacity in lymphocytes.

Original languageEnglish
JournalMutation Research - DNA Repair
Issue number3
Pages (from-to)197-210
Number of pages14
Publication statusPublished - 9 Nov 2000
Externally publishedYes
CitationsWeb of Science® Times Cited: No match on DOI

    Research areas

  • HCR: Host cell reactivation, NER: Nucleotide excision repair, PBS: Phosphate buffered saline, PHA: Phytohemagglutinin
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ID: 138027625