Induction of beta-polymerase mRNA by DNA-damaging agents in Chinese hamster ovary cells.

Abstract

Studies of mammalian cells with DNA polymerase inhibitors have suggested that 3-polymerase has a role in DNA repair (1,3,13,18,24), and the in vitro activity of purified ,-polymerase points to an in vivo role in resynthesis of short gaps after damaged residues have been excised (4,9,15,19,21,22). Lesions produced by several DNA-damaging agents are repaired by single-base excision or short-gap excision followed by resynthesis to fill the gap (8). It is unknown whether regulation of P-polymerase gene expression is correlated with DNA repair, although it is clear that levels of 3-polymerase mRNA do not correlate with stages of the cell cycle or with replication of genomic DNA (25a). A rodent cDNA for ,-polymerase was isolated recently (26), and we have used this DNA as a probe to study regulation of P-polymerase mRNA in Chinese hamster ovary (CHO) cells after treatment with a variety of DNA-damaging agents.We found that the level of ,B-polymerase mRNA in exponentially growing CHO cells is elevated three-to fivefold after treatment with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), methyl methanesulfonate (MMS), or N-acetoxy-2-acetylaminofluorene (AAAF) (Fig. 1). The results of quantitative RNA dot blot analyses (6, 7) after treatment with high levels of these and other agents are summarized in Table 1. For reference, dot blots also were probed with

Radiation‐induced gene expression profile of human cells deficient in 8‐hydroxy‐2′‐deoxyguanine glycosylase

“…Our data are consistent with other studies showing no increase of Polb after X-ray exposure. 35,36 Studies employing microarray technology have also found that repair genes are not upregulated after ionizing radiation exposure. 24,37 It is interesting to consider that if the adaptive response to ionizing radiation requires transcriptional activation, induction of BER genes may not be involved in radioadaptation.…”

Mutator phenotype of BCR – ABL transfected Ba/F3 cell lines and its association with enhanced expression of DNA polymerase β

“…It is a monomeric protein of 335 amino acids (39 kDa) that lacks exonuclease activities and appears to be the least accurate of the eukaryotic DNA polymerases in vitro (Kunkel, 1985). In vivo, it is expressed at a constant low level throughout the cell cycle (Zmudzka et al, 1988) and is inducible by some genotoxic treatments (Fornace et al, 1989). The increased mutation frequency we observed for the BCR ± ABL transfected Ba/F3 cells urged us to compare the expression of Pol b between the untransfected control Ba/F3 cells and the p190-and p210-transfected Ba/F3 cells.…”

Self-destruction and tolerance in resistance of mammalian cells to alkylation damage

“…The lack of specificity in the inducing signal urges caution, however. There are numerous damage-inducible transcripts in mammalian cells for which there is so far no apparent function: an example is DNA polymerase which is 'induced' in CHO cells by MNNG treatment (37) although the increased mRNA levels do not seem to be correlated with increased DNA polymerase activity. Indeed, unless the rate-limiting step for DNA repair is polymerization, increased DNA polymerase alone would be of little value.…”