G. P. Margison

Publication List Details

Period

1992 - 1992

Number

59

Co-Authors

Workshop on DNA repair. (1992)

Lehmann, A.R., Hoeijmakers, J.H.J., Zeeland, A.A. Van, Backendorf, C.M.P., Bridges, B.A., Collins, A., ...

A workshop on DNA repair with emphasis on eukaryotic systems was held, under the auspices of the EC Concerted Action on DNA Repair and Cancer, at Noordwijkerhout (The Netherlands) 14-19 April 1991....

Targeted deletion of alkylpurine-DNA-N-glycosylase in mice eliminates repair of 1,N6-ethenoadenine and hypoxanthine but not of 3,N4-ethenocytosine or 8-oxoguanine

Hang, B., Singer, B., Margison, G. P., Elder, R. H.

It has previously been reported that 1,N6-ethenoadenine (ɛA), deaminated adenine (hypoxanthine, Hx), and 7,8-dihydro-8-oxoguanine (8-oxoG), but not 3,N4-ethenocytosine (ɛC), are released from DNA...

Ribozyme minigene-mediated RAD51 down-regulation increases radiosensitivity of human prostate cancer cells

Collis, S. J., Tighe, A., Scott, S. D., Roberts, S. A., Hendry, J. H., Margison, G. P.

The strand transferase RAD51 is a component of the homologous recombination repair pathway. To examine the contribution of RAD51 to the genotoxic effects of ionising radiation, we have used a novel...

Relationship between O6-alkylguanine-DNA alkyltransferase activity and N-methyl-N'-nitro-N-nitrosoguanidine-induced mutation, transformation, and cytotoxicity in C3H/10T1/2 cells expressing exogenous alkyltransferase genes.

Von Hofe, E, Fairbairn, L, Margison, G P

While a great deal of evidence has directly implicated the importance of O6-alkylation of guanine in the mutagenicity of alkylating agents, evidence demonstrating the oncogenic potential of this...

Development of a novel rapid assay to assess the fidelity of DNA double-strand-break repair in human tumour cells

Collis, S. J., Sangar, V. K., Tighe, A., Roberts, S. A., Clarke, N. W., Hendry, J. H., ...

Cellular survival following ionising radiation-mediated damage is primarily a function of the ability to successfully detect and repair DNA double-strand breaks (DSBs). Previous studies have...

Identification and characterisation of the Drosophila melanogaster O6-alkylguanine-DNA alkyltransferase cDNA.

Kooistra, R, Zonneveld, J B, Watson, A J, Margison, G P, Lohman, P H, Pastink, A

The protein O 6-alkylguanine-DNA alkyltransferase(alkyltransferase) is involved in the repair of O 6-alkylguanine and O 4-alkylthymine in DNA and plays an important role in most organisms in...

Repair of O-alkylpyrimidines in mammalian cells: a present consensus.

Brent, T P, Dolan, M E, Fraenkel-Conrat, H, Hall, J, Karran, P, Laval, L, ...

Enzymatic repair of the O-alkylpyrimidines (O2- and O4-alkylthymine, O2-alkylcytosine) and alkyl phosphotriesters has been studied in Escherichia coli, and the two proteins involved, a glycosylase...

Characterisation and nucleotide sequence of ogt, the O6-alkylguanine-DNA-alkyltransferase gene of E. coli.

Potter, P M, Wilkinson, M C, Fitton, J, Carr, F J, Brennand, J, Cooper, D P, ...

The plasmid pO61 that was isolated from an E. coli genomic DNA library and codes for O6-alkylguanine (O6AG) DNA alkyltransferase (ATase) activity (1) has been further characterised. Subclones of the...

Expression of the E.coli ada gene in S.cerevisiae provides cellular resistance to N-methyl-N'-nitro-N-nitrosoguanidine in rad6 but not in rad52 mutants.

Brozmanová, J, Vlcková, V, Chovanec, M, Cernáková, L, Skorvaga, M, Margison, G P

The Escherichia coli ada gene protein coding region under the control of the yeast alcohol dehydrogenase promoter in the extrachromosomally replicating yeast expression vectors pADHO6C and pVT103LO6C...

Inducible alkyltransferase DNA repair proteins in the filamentous fungus Aspergillus nidulans.

Baker, S M, Margison, G P, Strike, P

We have investigated the response of the filamentous fungus Aspergillus nidulans to low, non-killing, doses of the alkylating agent MNNG (N-methyl-N'-nitro-N-nitrosoguanidine). Such treatment causes...

Isolation and partial characterisation of a Chinese hamster O6-alkylguanine-DNA alkyltransferase cDNA.

Rafferty, J A, Elder, R H, Watson, A J, Cawkwell, L, Potter, P M, Margison, G P

The cDNA encoding Chinese hamster O6-alkylguanine-DNA-alkyltransferase (ATase) has been isolated from a library prepared from RNA isolated from V79 lung fibroblasts which had an upregulated level of...

Enzymatic release of 7-methylguanine from methylated DNA by rodent liver extracts.

Margison, G P, Pegg, A E

Rat and hamster liver extracts were found to contain DNA glycosylases capable of removing 3-methyladenine and 7-methylguanine from methylated DNA. The activity of 7-methylguanine-DNA glycosylase was...

Purification to apparent homogeneity and partial amino acid sequence of rat liver O6-alkylguanine-DNA-alkyltransferase.

Wilkinson, M C, Cooper, D P, Southan, C, Potter, P M, Margison, G P

O6-alkylguanine-DNA-alkyltransferase (ATase) activity was increased in rat liver from 80 to 320 fmoles/mg total protein 48 h after administration of 2-acetylaminofluorene at 60 mg/kg body weight....

Expression of the E.coli ada gene in yeast protects against the toxic and mutagenic effects of N-methyl-N'-nitro-N-nitrosoguanidine.

Brozmanova, J, Kleibl, K, Vlckova, V, Skorvaga, M, Cernakova, L, Margison, G P

The E.coli ada gene protein coding region has been ligated into an extrachromosomally replicating yeast expression vector downstream of the yeast alcohol dehydrogenase gene promoter region to produce...

Evidence that covalent complex formation between BCNU-treated oligonucleotides and E. coli alkyltransferases requires the O6-alkylguanine function.

Gonzaga, P E, Harris, L, Margison, G P, Brent, T P

Chloroethylnitrosoureas (CENUs) are thought to induce cytotoxic DNA interstrand cross-links via an initial reaction at O6-position of guanine, yielding a rearranged intermediate, O6,N1-ethanoguanine....

Expression of a human O6-alkylguanine-DNA-alkyltransferase cDNA in human cells and transgenic mice.

Fan, C Y, Potter, P M, Rafferty, J, Watson, A J, Cawkwell, L, Searle, P F, ...

A truncated human O6-alkylguanine-DNA-alkyltransferase (ATase) cDNA was ligated into an expression vector under the control of the mouse metallothionein-1 gene promotor and upstream of part of the...

Expression of the ogt gene in wild-type and ada mutants of E. coli.

Potter, P M, Kleibl, K, Cawkwell, L, Margison, G P

O6-alkylguanine (O6-AlkG) DNA alkyltransferase (ATase) and alkylphosphotriester (AlkP) ATase activity have been quantitated individually in extracts of various E. coli strains by means of ATase...

Purification of the E. coli ogt gene product to homogeneity and its rate of action on O6-methylguanine, O6-ethylguanine and O4-methylthymine in dodecadeoxyribonucleotides.

Wilkinson, M C, Potter, P M, Cawkwell, L, Georgiadis, P, Patel, D, Swann, P F, ...

The E. coli gene ogt encodes the DNA repair protein O6-alkylguanine-DNA-alkyltransferase (O6-AlkG ATase). The protein coding region of the gene was cloned into a multicopy expression vector to obtain...

Cloning of the E. coli O6-methylguanine and methylphosphotriester methyltransferase gene using a functional DNA repair assay.

Margison, G P, Cooper, D P, Brennand, J

Alkylating agents react with various nitrogen and oxygen atoms in DNA and many of the products are substrates for repair processes. Oxygen atom derivatives such as O6-methylguanine (O6-meG)...

Reduction of the toxicity and mutagenicity of alkylating agents in mammalian cells harboring the Escherichia coli alkyltransferase gene.

Brennand, J, Margison, G P

The toxic, mutagenic, and carcinogenic effects of alkylating agents have been attributed to their ability to damage DNA. Reaction at the O6 position of guanine results in miscoding during DNA...

Expression of the E.coli 3-methyladenine DNA glycosylase I gene in mammalian cells reduces the toxic and mutagenic effects of methylating agents.

Klungland, A, Fairbairn, L, Watson, A J, Margison, G P, Seeberg, E

In order to investigate the importance of 3-methyladenine in cellular sensitivity to chemical methylating agents we have constructed retroviral vectors for the integration and expression of the...

C-terminally truncated human O6-alkylguanine-DNA alkyltransferase retains activity.

Elder, R H, Tumelty, J, Douglas, K T, Margison, G P, Rafferty, J A

A cDNA encoding the human O6-alkylguanine-DNA alkyltransferase (ATase; EC 2.1.1.63; methylated-DNA: protein-cysteine methyltransferase) has been manipulated to generate a C-terminally deleted protein...

Differential inactivation of mammalian and Escherichia coli O6-alkylguanine-DNA alkyltransferases by O6-benzylguanine.

Elder, R H, Margison, G P, Rafferty, J A

The action of O6-benzylguanine (O6-BzlG) on recombinant mammalian and Escherichia coli O6-alkylguanine-DNA alkyltransferases (ATase; EC 2.1.1.63; methylated-DNA-protein-cysteine methyltransferase)...

Methylated purines in the deoxyribonucleic acid of various Syrian-golden-hamster tissues after administration of a hepatocarcinogenic dose of dimethylnitrosamine.

Margison, G P, Margison, J M, Montesano, R

1. DNA was extracted from livers, kidneys and lungs of Syrian golden hamsters at various times (up to 96h) after injection of a hepatocarcinogenic dose of [14C]dimethylnitrosamine. Purine bases were...

Accumulation of O6-methylguanine in non-target-tissue deoxyribonucleic acid during chronic administration of dimethylnitrosamine.

Margison, G P, Margison, J M, Montesano, R

1. BD-IV rats were given labelled dimethylnitrosamine (2 mg/kg) by stomach tube on weekdays (Monday to Friday) for up to 24 weeks. The rats killed after 2, 4, 8, 16 and 24 weeks of treatment (72 h...

Chemical carcinogenesis in the nervous system. Preferential accumulation of O6-methylguanine in rat brain deoxyribonucleic acid during repetitive administration of N-methyl-N-nitrosourea.

Margison, G P, Kleihues, P

The alkylation of purine bases in DNA of several rat tissues was determined during weekly injections (10 mg/kg) of N-[3H]methyl-N-nitrosourea, a dose schedule known to selectively induce tumours of...

Role of apurinic sites in the resistance of methylated oligodeoxyribonucleotides to degradation by spleen exonuclease.

Margison, G P, O'Connor, P J

The effect of introducing methyl groups into DNA substrates was studied by using the spleen exonuclease (EC 3.1.4.1), an enzyme which hydrolyses oligonucleotides in a sequential manner by splitting...

Persistence of methylated bases in ribonucleic acid of syrian golden hamster liver after administration of dimethylnitrosamine.

Margison, G P, Margison, J M, Montesano, R

1. Syrian golden hamster liver ribosomal RNA was isolated up to 96 h after administration of [14C]dimethylnitrosamine at 25 mg/kg or 2.5 mg/kg body weight. 2. The chemical alkyation products,...

Targeted deletion of alkylpurine-DNA-N-glycosylase in mice eliminates repair of 1,N6-ethenoadenine and hypoxanthine but not of 3,N4-ethenocytosine or 8-oxoguanine

Hang, B., Singer, B., Margison, G. P., Elder, R. H.

It has previously been reported that 1,N6-ethenoadenine (ɛA), deaminated adenine (hypoxanthine, Hx), and 7,8-dihydro-8-oxoguanine (8-oxoG), but not 3,N4-ethenocytosine (ɛC), are released from DNA...

Ribozyme minigene-mediated RAD51 down-regulation increases radiosensitivity of human prostate cancer cells

Collis, S. J., Tighe, A., Scott, S. D., Roberts, S. A., Hendry, J. H., Margison, G. P.

The strand transferase RAD51 is a component of the homologous recombination repair pathway. To examine the contribution of RAD51 to the genotoxic effects of ionising radiation, we have used a novel...

Relationship between O6-alkylguanine-DNA alkyltransferase activity and N-methyl-N'-nitro-N-nitrosoguanidine-induced mutation, transformation, and cytotoxicity in C3H/10T1/2 cells expressing exogenous alkyltransferase genes.

Von Hofe, E, Fairbairn, L, Margison, G P

While a great deal of evidence has directly implicated the importance of O6-alkylation of guanine in the mutagenicity of alkylating agents, evidence demonstrating the oncogenic potential of this...

Development of a novel rapid assay to assess the fidelity of DNA double-strand-break repair in human tumour cells

Collis, S. J., Sangar, V. K., Tighe, A., Roberts, S. A., Clarke, N. W., Hendry, J. H., ...

Cellular survival following ionising radiation-mediated damage is primarily a function of the ability to successfully detect and repair DNA double-strand breaks (DSBs). Previous studies have...

Identification and characterisation of the Drosophila melanogaster O6-alkylguanine-DNA alkyltransferase cDNA.

Kooistra, R, Zonneveld, J B, Watson, A J, Margison, G P, Lohman, P H, Pastink, A

The protein O 6-alkylguanine-DNA alkyltransferase(alkyltransferase) is involved in the repair of O 6-alkylguanine and O 4-alkylthymine in DNA and plays an important role in most organisms in...

Repair of O-alkylpyrimidines in mammalian cells: a present consensus.

Brent, T P, Dolan, M E, Fraenkel-Conrat, H, Hall, J, Karran, P, Laval, L, ...

Enzymatic repair of the O-alkylpyrimidines (O2- and O4-alkylthymine, O2-alkylcytosine) and alkyl phosphotriesters has been studied in Escherichia coli, and the two proteins involved, a glycosylase...

Characterisation and nucleotide sequence of ogt, the O6-alkylguanine-DNA-alkyltransferase gene of E. coli.

Potter, P M, Wilkinson, M C, Fitton, J, Carr, F J, Brennand, J, Cooper, D P, ...

The plasmid pO61 that was isolated from an E. coli genomic DNA library and codes for O6-alkylguanine (O6AG) DNA alkyltransferase (ATase) activity (1) has been further characterised. Subclones of the...

Expression of the E.coli ada gene in S.cerevisiae provides cellular resistance to N-methyl-N'-nitro-N-nitrosoguanidine in rad6 but not in rad52 mutants.

Brozmanová, J, Vlcková, V, Chovanec, M, Cernáková, L, Skorvaga, M, Margison, G P

The Escherichia coli ada gene protein coding region under the control of the yeast alcohol dehydrogenase promoter in the extrachromosomally replicating yeast expression vectors pADHO6C and pVT103LO6C...

Inducible alkyltransferase DNA repair proteins in the filamentous fungus Aspergillus nidulans.

Baker, S M, Margison, G P, Strike, P

We have investigated the response of the filamentous fungus Aspergillus nidulans to low, non-killing, doses of the alkylating agent MNNG (N-methyl-N'-nitro-N-nitrosoguanidine). Such treatment causes...

Isolation and partial characterisation of a Chinese hamster O6-alkylguanine-DNA alkyltransferase cDNA.

Rafferty, J A, Elder, R H, Watson, A J, Cawkwell, L, Potter, P M, Margison, G P

The cDNA encoding Chinese hamster O6-alkylguanine-DNA-alkyltransferase (ATase) has been isolated from a library prepared from RNA isolated from V79 lung fibroblasts which had an upregulated level of...

Enzymatic release of 7-methylguanine from methylated DNA by rodent liver extracts.

Margison, G P, Pegg, A E

Rat and hamster liver extracts were found to contain DNA glycosylases capable of removing 3-methyladenine and 7-methylguanine from methylated DNA. The activity of 7-methylguanine-DNA glycosylase was...

Purification to apparent homogeneity and partial amino acid sequence of rat liver O6-alkylguanine-DNA-alkyltransferase.

Wilkinson, M C, Cooper, D P, Southan, C, Potter, P M, Margison, G P

O6-alkylguanine-DNA-alkyltransferase (ATase) activity was increased in rat liver from 80 to 320 fmoles/mg total protein 48 h after administration of 2-acetylaminofluorene at 60 mg/kg body weight....

Expression of the E.coli ada gene in yeast protects against the toxic and mutagenic effects of N-methyl-N'-nitro-N-nitrosoguanidine.

Brozmanova, J, Kleibl, K, Vlckova, V, Skorvaga, M, Cernakova, L, Margison, G P

The E.coli ada gene protein coding region has been ligated into an extrachromosomally replicating yeast expression vector downstream of the yeast alcohol dehydrogenase gene promoter region to produce...

Evidence that covalent complex formation between BCNU-treated oligonucleotides and E. coli alkyltransferases requires the O6-alkylguanine function.

Gonzaga, P E, Harris, L, Margison, G P, Brent, T P

Chloroethylnitrosoureas (CENUs) are thought to induce cytotoxic DNA interstrand cross-links via an initial reaction at O6-position of guanine, yielding a rearranged intermediate, O6,N1-ethanoguanine....

Expression of a human O6-alkylguanine-DNA-alkyltransferase cDNA in human cells and transgenic mice.

Fan, C Y, Potter, P M, Rafferty, J, Watson, A J, Cawkwell, L, Searle, P F, ...

A truncated human O6-alkylguanine-DNA-alkyltransferase (ATase) cDNA was ligated into an expression vector under the control of the mouse metallothionein-1 gene promotor and upstream of part of the...

Expression of the ogt gene in wild-type and ada mutants of E. coli.

Potter, P M, Kleibl, K, Cawkwell, L, Margison, G P

O6-alkylguanine (O6-AlkG) DNA alkyltransferase (ATase) and alkylphosphotriester (AlkP) ATase activity have been quantitated individually in extracts of various E. coli strains by means of ATase...

Purification of the E. coli ogt gene product to homogeneity and its rate of action on O6-methylguanine, O6-ethylguanine and O4-methylthymine in dodecadeoxyribonucleotides.

Wilkinson, M C, Potter, P M, Cawkwell, L, Georgiadis, P, Patel, D, Swann, P F, ...

The E. coli gene ogt encodes the DNA repair protein O6-alkylguanine-DNA-alkyltransferase (O6-AlkG ATase). The protein coding region of the gene was cloned into a multicopy expression vector to obtain...

Cloning of the E. coli O6-methylguanine and methylphosphotriester methyltransferase gene using a functional DNA repair assay.

Margison, G P, Cooper, D P, Brennand, J

Alkylating agents react with various nitrogen and oxygen atoms in DNA and many of the products are substrates for repair processes. Oxygen atom derivatives such as O6-methylguanine (O6-meG)...

Reduction of the toxicity and mutagenicity of alkylating agents in mammalian cells harboring the Escherichia coli alkyltransferase gene.

Brennand, J, Margison, G P

The toxic, mutagenic, and carcinogenic effects of alkylating agents have been attributed to their ability to damage DNA. Reaction at the O6 position of guanine results in miscoding during DNA...

Expression of the E.coli 3-methyladenine DNA glycosylase I gene in mammalian cells reduces the toxic and mutagenic effects of methylating agents.

Klungland, A, Fairbairn, L, Watson, A J, Margison, G P, Seeberg, E

In order to investigate the importance of 3-methyladenine in cellular sensitivity to chemical methylating agents we have constructed retroviral vectors for the integration and expression of the...

C-terminally truncated human O6-alkylguanine-DNA alkyltransferase retains activity.

Elder, R H, Tumelty, J, Douglas, K T, Margison, G P, Rafferty, J A

A cDNA encoding the human O6-alkylguanine-DNA alkyltransferase (ATase; EC 2.1.1.63; methylated-DNA: protein-cysteine methyltransferase) has been manipulated to generate a C-terminally deleted protein...

Differential inactivation of mammalian and Escherichia coli O6-alkylguanine-DNA alkyltransferases by O6-benzylguanine.

Elder, R H, Margison, G P, Rafferty, J A

The action of O6-benzylguanine (O6-BzlG) on recombinant mammalian and Escherichia coli O6-alkylguanine-DNA alkyltransferases (ATase; EC 2.1.1.63; methylated-DNA-protein-cysteine methyltransferase)...

Methylated purines in the deoxyribonucleic acid of various Syrian-golden-hamster tissues after administration of a hepatocarcinogenic dose of dimethylnitrosamine.

Margison, G P, Margison, J M, Montesano, R

1. DNA was extracted from livers, kidneys and lungs of Syrian golden hamsters at various times (up to 96h) after injection of a hepatocarcinogenic dose of [14C]dimethylnitrosamine. Purine bases were...

Accumulation of O6-methylguanine in non-target-tissue deoxyribonucleic acid during chronic administration of dimethylnitrosamine.

Margison, G P, Margison, J M, Montesano, R

1. BD-IV rats were given labelled dimethylnitrosamine (2 mg/kg) by stomach tube on weekdays (Monday to Friday) for up to 24 weeks. The rats killed after 2, 4, 8, 16 and 24 weeks of treatment (72 h...

Chemical carcinogenesis in the nervous system. Preferential accumulation of O6-methylguanine in rat brain deoxyribonucleic acid during repetitive administration of N-methyl-N-nitrosourea.

Margison, G P, Kleihues, P

The alkylation of purine bases in DNA of several rat tissues was determined during weekly injections (10 mg/kg) of N-[3H]methyl-N-nitrosourea, a dose schedule known to selectively induce tumours of...

Role of apurinic sites in the resistance of methylated oligodeoxyribonucleotides to degradation by spleen exonuclease.

Margison, G P, O'Connor, P J

The effect of introducing methyl groups into DNA substrates was studied by using the spleen exonuclease (EC 3.1.4.1), an enzyme which hydrolyses oligonucleotides in a sequential manner by splitting...

Persistence of methylated bases in ribonucleic acid of syrian golden hamster liver after administration of dimethylnitrosamine.

Margison, G P, Margison, J M, Montesano, R

1. Syrian golden hamster liver ribosomal RNA was isolated up to 96 h after administration of [14C]dimethylnitrosamine at 25 mg/kg or 2.5 mg/kg body weight. 2. The chemical alkyation products,...