Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.7 (DNA polymerase)
 17,007 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We demonstrate a successful induction of DNA single strand breaks in CHO-K1 cells by cocultivation with mouse embryonic fibroblasts (MEF) during exposure to benzo(a)pyrene (BP) or 3-methylcholanthrene (MC). When compared to those induced by methyl methanesulfonate (MMS), the DNA single strand breaks induced by BP and MC were markedly accumulated by post-incubation with cytosine arabinoside (araC) and were much more delayed in their rejoining. These results suggest that the active metabolites of BP or MC produced by cocultivation with MEF or microsomal fraction (S-15) result in the formation of large DNA adducts which require an active participation of DNA polymerase alpha(delta) in the polymerization step of excision repair for their removal.
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PMID:Accumulation of polycyclic aromatic hydrocarbon-induced single strand breaks is attributed to slower rejoining processes by DNA polymerase inhibitor, cytosine arabinoside in CHO-K1 cells. 200 53

Deficiency of apurinic/apyrimidinic (AP) DNA-repair enzymes in crude extracts of E. coli mutants was determined by following general and specific AP DNA-repair synthesis via nick translation in the presence of either all four dNTPs, or only one dNTP. We have shown that mutations either in DNA polymerase I or in AP endonucleases or in both, inhibit to different degrees the ability to repair AP DNA. The polA mutation totally abolishes the ability to perform both general and specific AP DNA repair, while the polAex mutation affects only general AP DNA repair. The xthA tight mutants, including the deletion mutant BW9101, can cope with small amounts of AP sites but hardly with high amounts of these lesions. In addition we have found that crude extracts of the xthA mutants degrade AP DNA by two modes: a nonspecific, and an AP-specific mode. These phenomena are common to all xth mutants and enabled us to discover this mutation. In contrast to the xth mutants so far isolated, BW2001 exhibits marked sensitivity to MMS and to X-ray irradiation. We found that this strain has a proficient DNA polymerase I but is absolutely deficient in AP endonucleases. We attribute its sensitivities to a secondary mutation at the structural gene of endonuclease IV.
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PMID:Characterization of Escherichia coli mutant strains deficient in AP DNA-repair synthesis. 242 76

The pcbA1 mutation allows DNA replication dependent on DNA polymerase I at the restrictive temperature in polC(Ts) strains. Cells which carry pcbA1, a functional DNA polymerase I, and a temperature-sensitive DNA polymerase III gene were used to study the role of DNA polymerase III in DNA repair. At the restrictive temperature for DNA polymerase III, these strains were more sensitive to the alkylating agent methyl methanesulfonate (MMS) and hydrogen peroxide than normal cells. The same strains showed no increase in sensitivity to bleomycin, UV light, or psoralen at the restrictive temperature. The sensitivity of these strains to MMS and hydrogen peroxide was not due to the pcbAl allele, and normal sensitivity was restored by the introduction of a chromosomal or cloned DNA polymerase III gene, verifying that the sensitivity was due to loss of DNA polymerase III alpha-subunit activity. A functional DNA polymerase III is required for the reformation of high-molecular-weight DNA after treatment of cells with MMS or hydrogen peroxide, as demonstrated by alkaline sucrose sedimentation results. Thus, it appears that a functional DNA polymerase III is required for the optimal repair of DNA damage by MMS or hydrogen peroxide.
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PMID:DNA polymerase III requirement for repair of DNA damage caused by methyl methanesulfonate and hydrogen peroxide. 244 82

We have shown that the level of DNA polymerase I (Pol I) activity in Escherichia coli is influenced by the level of a 109-nucleotide RNA, spot 42 RNA. Deletion of the gene for spot 42 RNA results in a 20 to 25% decrease in Pol I activity, as assayed by nucleotide incorporation in cell extracts and a decrease in the ability of cells to grow in the presence of the DNA-alkylating agent methyl methanesulfonate. Also, a physiological reduction of the level of spot 42 RNA, by growth in media containing poor carbon sources, results in a corresponding decrease in Pol I activity. Conversely, overproduction of spot 42 RNA results in a 10 to 15% increase in Pol I activity in vitro. Thus, changes in the amount of spot 42 RNA result in relatively small but significant changes in Pol I activity.
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PMID:DNA polymerase I activity in Escherichia coli is influenced by spot 42 RNA. 245 53

In Escherichia coli the dnaQ+ gene, which encodes epsilon, a fidelity subunit of DNA polymerase III, and the rnh+ gene, which encodes RNase H, share a promoter region but are transcribed in opposite directions. The presence of this divergent transcriptional unit on a multicopy plasmid inhibited by as much as 10-fold mutations induced by the SOS-dependent mutagens methyl methanesulfonate and UV light. Mutations in either gene eliminated the effect, suggesting that both genes contribute either directly or indirectly to the antimutagenic phenotype. Neither survival to mutagen exposure nor induction of the SOS response was comparably affected by the presence of the genes. Although the antimutagenic phenotype was partially suppressed by excess UmuDC proteins, which are required for SOS mutagenesis, the presence of the dnaQ+-rnh+ clone also reduced the induction of mutations by N-methyl-N'-nitro-N-nitrosoguanidine in cells deficient for SOS mutagenic processing. The results suggest that the presence of the dnaQ+-rnh+ divergent transcriptional unit interferes with an underlying mutagenic mechanism that is normally facilitated by the proteins induced as part of the SOS response.
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PMID:Presence of the dnaQ-rnh divergent transcriptional unit on a multicopy plasmid inhibits induced mutagenesis in Escherichia coli. 254 18

The value of the unscheduled DNA synthesis after the combined effect of UV radiation and methyl methanesulfonate (MMS) was considerably lower than that upon exposure to UV radiation alone and after two-hour incubation of the culture. These differences were insignificant after 26 h incubation. The result can be attributed to the alkylating effect of MMS on the repair DNA polymerase. With MMS delivered prior to UV irradiation there was an even larger decrease in the unscheduled DNA synthesis with both 2- and 26-hour incubation. The data obtained can be explained by the fact that MMS inhibits an excision endonuclease.
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PMID:[The modifying action of methylmethane sulfonate on unscheduled DNA synthesis in the UV irradiation of human peripheral blood lymphocytes]. 278 Sep 92

The rate of intracellular ligation of excision-repair patches has been measured under conditions of inhibition of poly(ADP-ribose) synthesis by 3-aminobenzamide. Excision-repair patches in DNA of cells damaged by methyl methanesulfonate were labeled with [3H]thymidine and blocked at an intermediate stage by aphidicolin, an inhibitor of DNA polymerase alpha. Removal of [3H]thymidine and aphidicolin permitted the intracellular ligation rate to be determined by rapid digestion of [3H]-labeled 3' termini with exonuclease III. Contrary to previous conclusions from more indirect experiments, inhibition of poly(ADP-ribose) synthesis by 3-aminobenzamide actually facilitates rapid ligation.
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PMID:Enhanced ligation of repair sites under conditions of inhibition of poly(ADP-ribose) synthesis by 3-aminobenzamide. 308 4

The rate of intracellular ligation of excision repair patches has been measured under conditions of inhibition of poly(ADP-ribose) synthesis by 3-aminobenzamide. Excision repair patches in DNA of cells damaged by methyl methanesulfonate were labeled with [3H]thymidine and blocked at an intermediate stage by aphidicolin, an inhibitor of DNA polymerase alpha. Nearly half of the [3H]thymidine label in the repair patches was sensitive to rapid digestion by exonuclease III, indicating that the label was at unligated 3' termini of repair sites. Removal of [3H]thymidine and aphidicolin permitted the intracellular ligation rate to be determined. From analysis of chromatin, ligation appeared to occur rapidly, independent of the effect of 3-aminobenzamide. Analysis of purified DNA, however, indicated that high doses of methyl methanesulfonate resulted in slow ligation rates but that 3-aminobenzamide accelerated the rates of ligation. The analysis of chromatin, therefore, indicates that unligated repair sites are sites of protein accretion which block exonuclease III action. The results from analysis of DNA indicate that poly(ADP-ribose) synthesis and associated pool depletion inhibits ligation rates; 3-aminobenzamide prevents poly(ADP-ribose) synthesis, maintains pool levels high and facilitates rapid ligation.
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PMID:DNA ligation and changes in chromatin structure associated with repair patches under conditions of inhibition of poly(ADP-ribose) synthesis. 308 71

The polA gene of Streptococcus pneumoniae cloned in the recombinant plasmid pSM22 is expressed in Bacillus subtilis. Extracts of B. subtilis polA mutants containing pSM22 showed 6 times more DNA polymerase activity than extracts of wild-type cells without the plasmid. Complete complementation of the B. subtilis polA5 and polA59 mutations with respect to in vivo resistance to UV irradiation and methyl methanesulfonate was observed when four copies of the pneumococcal polA gene were present in each cell. Ectopic integration of the polA gene together with a cat marker into the chromosome of B. subtilis gave chromosomal insertions containing single and double doses of the pneumococcal polA gene. Correlation with gene dosage was observed for both chloramphenicol acetyltransferase and DNA polymerase activities measured in vitro. Depending on the number of copies of the S. pneumoniae polA gene present, restoration of DNA repair functions in polA mutants of B. subtilis was either partial or complete.
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PMID:Complementation of Bacillus subtilis polA mutants by DNA polymerase I from Streptococcus pneumoniae. 312 7

Scheduled (SDS) and unscheduled (UDS) DNA synthesis as well as nucleoid sedimentation was investigated in vitro under the influence of novobiocin (NB) and nalidixic acid (NA) using intact thymic (T-cells) and splenic (S-cells) rat cells and cells which were exposed to X-rays, UV irradiation, methyl methanesulfonate (MMS), and DNA polymerase inhibitors. At concentrations of greater than or equal to 56.25 (S-cells) and greater than or equal to 225 micrograms/ml (T-cells), respectively, NB inhibited SDS in a dose-dependent manner. Within a concentration range of greater than or equal to 225-900 micrograms NB/ml, UDS of S-cells decreased to values far below the tracer ([3H-methyl]-thymidine) incorporation of control cells, whereas UDS of T-cells increased by at least 200%. Within a concentration range of 450-1800 micrograms/ml, NA enhanced SDS and UDS by about 30% in S-cells and by 100% in T-cells. The stimulating activity of NB and/or NA could be eliminated specifically by the DNA polymerase beta inhibitor 2',3'-dideoxythymidine. Enhanced nucleoid sedimentation was observed at NB concentrations greater than or equal to 750 micrograms/ml; S-cells revealed a higher sedimentation rate than T-cells. It is suggested that NB (and NA) influence DNA topology in a rather cell specific manner, stimulating UDS of T-cells by a DNA polymerase beta - dependent repair-like mechanism.
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PMID:Stimulation of DNA repair synthesis of rat thymocytes by novobiocin and nalidixic acid in vitro without detectable DNA damage. 363 53


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