Mammalian cells share a common pathway for the relief of DNA replication arrest by O6-alkyl guanine, incorporated 6-thioguanine and UV photoproducts

D. B. Godfrey, Simon Bouffler, S. R.R. Musk, M. J. Raman, R. T. Johnson

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

We previously reported the cloning of a mammalian gene that restores UV resistance to a postreplication recovery defective and mex- Indian muntjac mutant cell line, SVM, by improving daughter-strand DNA replication on a UV-damaged template. The improved replication was, however, found to be error-prone, as judged by a hypermutable phenotype (Bouffler et al. (1990) Somatic Cell Mol. Genet., 16, 507-516). We now report that this gene also increases the resistance of SVM to the cytotoxic effects of methyl- and ethyl-nitrosourea, though not to dimethyl sulphate, by a similar postreplication recovery process. Thet gene does not increase the activity of O6-alkylguanine-DNA-alkyltransferase in the cell. We conclude that at least one mechanism of postreplication recovery in mammalian cells allows UV photoproducts and O6-alkylguanine lesions to be tolerated by the replication complex. The fact that the gene also confers resistance to 6-thioguanine suggests that, once incorporated, this base analogue can disrupt normal DNA replication and that a single mechanism can allow replication to proceed beyond 3 diverse DNA lesions.

Original languageEnglish
Pages (from-to)225-235
Number of pages11
JournalMutation Research-DNA Repair
Volume274
Issue number3
DOIs
Publication statusPublished - Sep 1992

Keywords

  • DNA alkyltransferase
  • DNA replication arrest
  • Mammalian cells
  • O-Alkyl guanine

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