Nucleic Acids Research, 2001, Vol. 29, No. 8 1791-1800
© 2001 Oxford University Press
Nucleotide excision repair in rat male germ cells: low level of repair in intact cells contrasts with high dual incision activity in vitro
1MGC—Department of Radiation Genetics and Chemical Mutagenesis, Leiden University Medical Center, Wassenaarseweg 72, 2333 AL Leiden, The Netherlands, 2Department of Environmental Medicine, National Institute of Public Health, PO Box 4404 Torshov, N-0403 Oslo, Norway, 3Institute of Pharmacology and Toxicology, University of Zürich-TierSpital, Winterhurstrasse 260, 8057 Zürich, Switzerland, 4Department of Genetics, Wageningen Institute of Animal Sciences, Wageningen University, The Netherlands and 5J.A. Cohen Institute, Interuniversity Research Institute for Radiopathology and Radiation Protection, Leiden, The Netherlands
The acquisition of genotoxin-induced mutations in the mammalian germline is detrimental to the stable transfer of genomic information. In somatic cells, nucleotide excision repair (NER) is a major pathway to counteract the mutagenic effects of DNA damage. Two NER subpathways have been identified, global genome repair (GGR) and transcription-coupled repair (TCR). In contrast to somatic cells, little is known regarding the expression of these pathways in germ cells. To address this basic question, we have studied NER in rat spermatogenic cells in crude cell suspension, in enriched cell stages and within seminiferous tubules after exposure to UV or N-acetoxy-2-acetylaminofluorene. Surprisingly, repair in spermatogenic cells was inefficient in the genome overall and in transcriptionally active genes indicating non-functional GGR and TCR. In contrast, extracts from early/mid pachytene cells displayed dual incision activity in vitro as high as extracts from somatic cells, demonstrating that the proteins involved in incision are present and functional in premeiotic cells. However, incision activities of extracts from diplotene cells and round spermatids were low, indicating a stage-dependent expression of incision activity. We hypothesize that sequestering of NER proteins by mispaired regions in DNA involved in synapsis and recombination may underlie the lack of NER activity in premeiotic cells.
* To whom correspondence should be addressed at: MGC—Department of Radiation Genetics and Chemical Mutagenesis, Leiden University Medical Center, Wassenaarseweg 72, 2333 AL Leiden, The Netherlands. Tel: +31 071 5276126; Fax: +31 071 5221615; Email: l.mullenders{at}lumc.nlThe authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors
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