DNA repair genes of mammalian cells.

L. H. Thompson, K. W. Brookman, E. P. Salazar, J. C. Fuscoe, C. A. Weber

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

In the Chinese hamster ovary (CHO) cell line, various mutations affecting DNA repair have been obtained. Mutants that belong to 5 genetic complementation groups for ultraviolet (UV) sensitivity and resemble the cells from individuals having the cancer-prone genetic disorder xeroderma pigmentosum (XP) were previously identified. Each mutant is defective in the incision step of nucleotide excision repair and hypersensitive to bulky DNA lesions. These UV mutants can be divided into two subgroups; only Groups 2 and 4 are extremely sensitive to mitomycin C and other DNA cross-linking agents. The clear-cut phenotypes of the CHO mutants have allowed us to construct hybrid cells by fusion with human lymphocytes and thereby identify which human chromosomes carry genes that correct the CHO mutations. The first two mutations analyzed, UV20 (excision-repair deficient; UV Group 2) and EM9, which has a very high frequency of sister chromatid exchange (SCE), are both corrected by chromosome 19. Efforts are underway to isolate complementing repair genes by DNA-mediated gene transfer. The human gene that corrects mutant EM9 and the hamster gene that corrects UV135 (UV Group 5) have been introduced by cotransfer of genomic DNA and the dominant selectable marker gpt (guanine phosphoribosyltransferase) gene. In each case, the DNA repair function was co-selected based on resistance to 5-chlorodeoxyuridine (CldUrd) or repeated UV irradiation, respectively. The presence of a functional human repair gene in the EM9 transformants is shown by the presence of common human DNA sequences on some fragments produced by restriction enzyme cleavage. In UV135, transfer of a repair gene is indicated by a colony distribution containing "jackpots" and by instability of the resistant phenotype.

Original languageEnglish (US)
Pages (from-to)349-358
Number of pages10
JournalBasic Life Sciences
Volume39
StatePublished - 1986
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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    Thompson, L. H., Brookman, K. W., Salazar, E. P., Fuscoe, J. C., & Weber, C. A. (1986). DNA repair genes of mammalian cells. Basic Life Sciences, 39, 349-358.