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Istituto di Genetica Biochimica ed Evoluzionistica C.N.R., via Abbiategrasso, 207-27100 Pavia, Italy [M. S., R. R., E. B., F. N.]; Department of Molecular and Cell Biology, University of Aberdeen, Marischal College, Aberdeen AB9 1AS, Scotland, United Kingdom [A. R. C., M. K.]; and Laboratory of Radiobiology and Environmental Health, University of California, San Francisco, California 94143-0750 [D. L. M.]
In this paper we demonstrate that the mutants CHO7PV and CHO4PV isolated by us from the CHO-K1 prol- cell line represent two new complementation groups of UV-sensitive excision repair-defective rodent mutants. We have classified the mutant CHO7PV as representative of Group 9 and CHO4PV as representative of Group 10. Cellular and biochemical characterization of these mutants indicates that they are moderately sensitive to a broad spectrum of mutagens (UV and mono- and bifunctional alkylating agents), partially unable to perform UV-induced DNA repair synthesis, and partially defective in the incision step of the DNA excision repair pathway and in the removal of the two main lesions caused by UV [cyclobutane pyrimidine dimers and (64) photo-products]. In terms of UV survival and incision, CHO4PV is apparently more defective than CHO7PV (40% and 50% of wild-type survival, respectively, and 55% and 75% of wild-type incision), whereas when repair DNA synthesis and lesion removal are compared, CHO7PV seems to be more severely affected (30% of wild-type unscheduled DNA synthesis in CHO7PV and 60% in CHO4PV). This suggests a subtlety in the relation between removal of these specific lesions and overall repair capacity and survival.
1 Supported by grants from the National Research Council of Italy (CNR Target Project Ingegneria Genetica), from the Commission of European Communities (Contract Bi7-034), and from the Cancer Research Campaign.
2 To whom requests for reprints should be addressed.
3 Michael Sobell Research Fellow.
4 Recipient of a fellowship from the Associazione Italiana per la Ricerca sul Cancro.
5 Alexander Hollaender Distinguished Postdoctoral Fellow sponsored by the US Department of Energy and by USPHS Grant CA15605. Present address: The University of Texas M. D. Anderson Cancer Center, Science Park-Research Division, Smithville, TX 78957.
Received 1/17/91. Accepted 5/15/91.
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