Geoffrey P. Margison

O6-Methylguanine-DNA methyltransferase inactivation and chemotherapy (2008)

Verbeek, Barbara, Southgate, Thomas D., Gilham, David E., Margison, Geoffrey P.

Introduction Alkylating agents are frequently used in the chemotherapy of many types of cancer. This group of drugs mediates cell death by damaging DNA and therefore, understandably, cellular DNA...

Targeting human 8-oxoguanine DNA glycosylase (hOGG1) to mitochondria enhances cisplatin cytotoxicity in hepatoma cells (2007)

Zhang, Haihong, Mizumachi, Takatsugu, Carcel-Trullols, Jaime, Li, Liwen, Naito, Akihiro, Spencer, Horace J., ...

Many chemoradiation therapies cause DNA damage through oxidative stress. An important cellular mechanism that protects cells against oxidative stress involves DNA repair. One of the primary DNA...

Multicistronic lentiviral vectors containing the FMDV 2A cleavage factor demonstrate robust expression of encoded genes at limiting MOI (2006)

Chinnasamy, Dhanalakshmi, Milsom, Michael D, Shaffer, James, Neuenfeldt, James, Shaaban, Aimen F, Margison, Geoffrey P, ...

Abstract Background A number of gene therapy applications would benefit from vectors capable of expressing multiple genes. In this study we explored the feasibility and efficiency of expressing two...

Novel synthesis of O6-alkylguanine containing oligodeoxyribonucleotides as substrates for the human DNA repair protein, O6-methylguanine DNA methyltransferase (MGMT) (2006)

Shibata, Takayuki, Glynn, Nicola, McMurry, T. Brian H., McElhinney, R. Stanley, Margison, Geoffrey P., Williams, David M.

The human DNA repair protein O6-methylguanine DNA methyltransferase (MGMT) dealkylates mutagenic O6-alkylguanine lesions within DNA in an irreversible reaction which results in inactivation of the...

Quantitative trait locus analysis reveals two intragenic sites that influence O6-alkylguanine-DNA alkyltransferase activity in peripheral blood mononuclear cells (2005)

Margison, Geoffrey P., Heighway, Jim, Pearson, Steven, McGown, Gail, Thorncroft, Mary R., Watson, Amanda J., ...

The repair of specific types of DNA alkylation damage by O6-alkylguanine-DNA alkyltransferase (MGMT) is a major mechanism of resistance to the carcinogenic and chemotherapeutic effects of certain...

Quantitative trait locus analysis reveals two intragenic sites that influence O6-alkylguanine-DNA alkyltransferase activity in peripheral blood mononuclear cells (2005)

Margison, Geoffrey P., Heighway, Jim, Pearson, Steven, McGown, Gail, Thorncroft, Mary R., Watson, Amanda J., ...

The repair of specific types of DNA alkylation damage by O6-alkylguanine-DNA alkyltransferase (MGMT) is a major mechanism of resistance to the carcinogenic and chemotherapeutic effects of certain...

Reduced MGMT activity in human colorectal adenomas is associated with K-ras GC->AT transition mutations in a population exposed to methylating agents (2004)

Lees, Nicholas P., Harrison, Kathryn L., Hall, C. Nick, Margison, Geoffrey P., Povey, Andrew C.

There is increasing evidence to suggest that O6-alkyl guanine DNAalkyltransferase (MGMT) activity provides protection against alkylating agent induced formation of GC→AT transition mutations in the...

Reduced MGMT activity in human colorectal adenomas is associated with K-ras GC->AT transition mutations in a population exposed to methylating agents (2004)

Lees, Nicholas P., Harrison, Kathryn L., Hall, C. Nick, Margison, Geoffrey P., Povey, Andrew C.

There is increasing evidence to suggest that O6-alkyl guanine DNA-alkyltransferase (MGMT) activity provides protection against alkylating agent induced formation of GC→AT transition mutations in...

Variability and regulation of O6-alkylguanine-DNA alkyltransferase (2003)

Margison, Geoffrey P., Povey, Andrew C., Kaina, Bernd, Santibáñez Koref, Mauro F.

O6-Alkylguanine–DNA alkyltransferase (ATase) confers resistance to many of the biological effects of certain classes of alkylating agents by repairing the DNA lesions responsible. The role of ATase...

Associations between tissue-specific DNA alkylation, DNA repair and cell proliferation in the colon and colon tumour yield in mice treated with 1,2-dimethylhydrazine (2003)

Jackson, Peta E., O’Connor, Peter J., Cooper, Donald P., Margison, Geoffrey P., Povey, Andrew C.

Putative risk factors (DNA damage) and risk modifying factors (DNA repair and cell proliferation) were examined in an experimental mouse model in which treatment with dimethylhydrazine (6.8 mg/kg DMH...

Mechanisms of carcinogenicity/chemotherapy by O6-methylguanine (2002)

Margison, Geoffrey P., Santibáñez Koref, Mauro F., Povey, Andrew C.

Alkylating agents are a structurally diverse group of compounds that cause a wide range of biological effects, including cell death, mutation and cancer. DNA damaged by these agents contains widely...

ETHANOL MODULATES RAT HEPATIC DNA REPAIR FUNCTIONS (2001)

Navasumrit, Panida, Margison, Geoffrey P., O'Connor, Peter J.

— To further explore how ethanol may act at the DNA level, studies have been made of DNA repair mechanisms in male Wistar rats given ethanol either as an acute intragastric dose (5 g/kg) or...

In vivo administration of O6-benzylguanine does not influence apoptosis or mutation frequency following DNA damage in the murine intestine, but does inhibit P450-dependent activation of dacarbazine (2000)

Toft, Neil J., Sansom, Owen J., Brookes, Roger A., Arends, Mark J., Wood, Michelle, Margison, Geoffrey P., ...

Clinically relevant cancer chemotherapeutic alkylating agents such as temozolomide and dacarbazine induce apoptosis and are mutagenic via the formation of O6-alkylguanine adducts in DNA. The DNA...

Contribution of ogt-encoded alkyltransferase to resistance to chloroethylnitrosoureas in nucleotide excision repair-deficient Escherichia coli (1996)

Abril, Nieves, Ferrezuelo, Francisco, Prieto-Alamo, Maria-Jose, Rafferty, Joseph A., Margison, Geoffrey P., Pueyo, Carmen

We investigated the relative contribution of the two Escherichia coli DNA alkyltransferases (ATases) to the increased sensitivity of ATase-deficient bacteria to the mutagenic and lethal effects of...

Expression of the E.coli ada gene in S.cerevisiae provides cellular resistance to /V-methyl-A/'-nitro-A/-nitrosoguanidine in rad6 but not in rad52 mutants (1994)

Brozmanovaá, Jela, Vlckovaá, Viera, Chovanec, Miroslav, Cernaákovaá, Lubica, Skorvaga, Milan, Margison, Geoffrey P.

The Escherichla coll ada gene protein coding region under the control of the yeast alcohol dehydrogenase promoter In the extrachromosomally replicating yeast expression vectors pADHO6C and pvT103LO6C...

Ionizing radiation induces O6-alkylguanine-DNA-alkyltransferase mRNA and activity in mouse tissues (1993)

Wilson, Rosemary E., Hoey, Brigid, Margison, Geoffrey P.

The effect of exposure to whole-body γ-irradiation or fast electrons on O6-alkylguanine-DNA-alkyltransferase (ATase) activity and mRNA abundance has been examined in mice. In response to...

Tissue and cell specific methylation, repair and synthesis of DNA in the upper gastrointestinal tract of Wistar rats treated with single doses of N-methyl-N'-nitro-N-nitrosoguanidine (1993)

Zaidi, Nasir H., Potten, Christopher S., Margison, Geoffrey P., Cooper, Donald P., O'Connor, Peter J.

Several potential cancer risk factors have been monitored concurrently in the upper gastrointestinal tract of young adult male Wistar rats given single (i.g.) doses of...

Tissue and cell specific methylation, repair and synthesis of DNA in the upper gastrointestinal tract of Wistar rats treated with N-methyl-N'-nitro-N-nitrosoguanidine via the drinking water (1993)

Zaidi, Nasir H., Potten, Christopher S., Margison, Geoffrey P., Cooper, Donald P., O'Connor, Peter J.

Several potential cancer risk factors have been monitored concurrently in the upper gastrointestinal tract of young male Wistar rats given N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) via the drinking...

Isolation and partial characterisation of a Chinese hamster O6-alkylguanine-DNA alky It ransferase cDNA (1992)

Rafferty, Joseph A., Elder, Rhoderick H., Watson, Amanda J., Cawkwell, Lynn, Potter, Philip M., Margison, Geoffrey P.

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

Evidence that covalent complex formation between BCNU treated oligonucleotides and E.coli alkyItransferases requires the O6-alkylguanine function (1990)

Gonzaga, Prescilla E., Harris, Linda, Margison, Geoffrey P., Brent, Thomas 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,...

Increased O6-alkylguanine alkyltransferase activity in Chinese hamster V79 cells following selection with chloroethylating agents (1988)

Morten, John E.N., Margison, Geoffrey P.

Chinese hamster V79 lung fibroblasts express low levels (specific activity 2–4 fmol/mg protein) of O6-alkylguanine (O6-AG) alkyltransferase (ATase). In cells surviving selection with low doses...

Expression in mammalian cells of a truncated Escherichia coli gene coding for O6-alkylguanine alkyltransferase reduces the toxic effects of alkylating agents (1986)

Brennand, John, Margison, Geoffrey P.

The lesion O6-alkylguanine (O6-AG) is produced in cellular DNA following exposure to monofunctional alkylating agents and its miscoding and mutagenic properties have been demonstrated in specific in...

Expression of the E. coli O6-methylguanine-methylphosphotriester methyltransferase gene in mammalian cells (1986)

Brennand, John, Margison, Geoffrey P.

Many prokaryotic and eukaryotic cells contain enzymes that repair damage introduced into their DNA following exposure to chemical, physical and biological agents. One such lesion that has received...

Cloning of the E. coli O6-methylguanine and methylphosphotriester methyltransferase gene using a functional DNA repair assay (1985)

Margison, Geoffrey P., Cooper, Donald P., Brennand, John

Akylating agents react with various nitrogen and oxygen atoms in DNA and many of the products are substrates repair processes. Oxygen atom derivatives such as 06 -methylguanine (06 -meG) 04...

Msh2 status modulates both apoptosis and mutation frequency in the murine small intestine

Toft, Neil J., Winton, Douglas J., Kelly, Jane, Howard, Louise A., Dekker, Marleen, Te Riele, Hein, ...

Deficiency in genes involved in DNA mismatch repair increases susceptibility to cancer, particularly of the colorectal epithelium. Using Msh2 null mice, we demonstrate that this genetic defect...

Thermostable archaeal O6-alkylguanine-DNA alkyltransferases

Skorvaga, Milan, Raven, Neil D. H., Margison, Geoffrey P.

Archaea represent some of the most ancient organisms on earth, and they have relatively uncharacterized DNA repair processes. We now show, using an in vitro assay, that extracts of two Crenarchaeota...

Increased Susceptibility to Streptozotocin-Induced β-Cell Apoptosis and Delayed Autoimmune Diabetes in Alkylpurine- DNA-N-Glycosylase-Deficient Mice

Cardinal, John W., Margison, Geoffrey P., Mynett, Kurt J., Yates, Allen P., Cameron, Donald P., Elder, Rhoderick H.

Type 1 diabetes is thought to occur as a result of the loss of insulin-producing pancreatic β cells by an environmentally triggered autoimmune reaction. In rodent models of diabetes, streptozotocin...

Alkylpurine–DNA–N-Glycosylase Knockout Mice Show Increased Susceptibility to Induction of Mutations by Methyl Methanesulfonate

Elder, Rhoderick H., Jansen, Jacob G., Weeks, Robert J., Willington, Mark A., Deans, Bryan, Watson, Amanda J., ...

Alkylpurine-DNA-N-glycosylase (APNG) null mice have been generated by homologous recombination in embryonic stem cells. The null status of the animals was confirmed at the mRNA level by reverse...

Inhibition of O6-methylguanine-DNA methyltransferase by an alkyltransferase-like protein from Escherichia coli

Pearson, Steven J., Ferguson, Jennifer, Santibanez-Koref, Mauro, Margison, Geoffrey P.

The alkyltransferase-like (ATL) proteins contain primary sequence motifs resembling those found in DNA repair O6-alkylguanine-DNA alkyltransferase proteins. However, in the putative active site of...

Are There Low-Penetrance TP53 Alleles? Evidence from Childhood Adrenocortical Tumors

Varley, Jennifer M., McGown, Gail, Thorncroft, Mary, James, Louise A., Margison, Geoffrey P., Forster, Gill, ...

We have analyzed a panel of 14 cases of childhood adrenocortical tumors unselected for family history and have identified germline TP53 mutations in >80%, making this the highest known incidence of a...

Novel synthesis of O6-alkylguanine containing oligodeoxyribonucleotides as substrates for the human DNA repair protein, O6-methylguanine DNA methyltransferase (MGMT)

Shibata, Takayuki, Glynn, Nicola, McMurry, T. Brian H., McElhinney, R. Stanley, Margison, Geoffrey P., Williams, David M.

The human DNA repair protein O6-methylguanine DNA methyltransferase (MGMT) dealkylates mutagenic O6-alkylguanine lesions within DNA in an irreversible reaction which results in inactivation of the...

Multicistronic lentiviral vectors containing the FMDV 2A cleavage factor demonstrate robust expression of encoded genes at limiting MOI

Chinnasamy, Dhanalakshmi, Milsom, Michael D, Shaffer, James, Neuenfeldt, James, Shaaban, Aimen F, Margison, Geoffrey P, ...

A novel DNA damage recognition protein in Schizosaccharomyces pombe

Pearson, Steven J., Wharton, Stephen, Watson, Amanda J., Begum, Ghazala, Butt, Amna, Glynn, Nicola, ...

Toxic and mutagenic O6-alkylguanine adducts in DNA are repaired by O6-alkylguanine-DNA alkyltransferases (MGMT) by transfer of the alkyl group to a cysteine residue in the active site. Comparisons in...

Msh2 status modulates both apoptosis and mutation frequency in the murine small intestine

Toft, Neil J., Winton, Douglas J., Kelly, Jane, Howard, Louise A., Dekker, Marleen, Te Riele, Hein, ...

Deficiency in genes involved in DNA mismatch repair increases susceptibility to cancer, particularly of the colorectal epithelium. Using Msh2 null mice, we demonstrate that this genetic defect...

Thermostable archaeal O6-alkylguanine-DNA alkyltransferases

Skorvaga, Milan, Raven, Neil D. H., Margison, Geoffrey P.

Archaea represent some of the most ancient organisms on earth, and they have relatively uncharacterized DNA repair processes. We now show, using an in vitro assay, that extracts of two Crenarchaeota...

Increased Susceptibility to Streptozotocin-Induced β-Cell Apoptosis and Delayed Autoimmune Diabetes in Alkylpurine- DNA-N-Glycosylase-Deficient Mice

Cardinal, John W., Margison, Geoffrey P., Mynett, Kurt J., Yates, Allen P., Cameron, Donald P., Elder, Rhoderick H.

Type 1 diabetes is thought to occur as a result of the loss of insulin-producing pancreatic β cells by an environmentally triggered autoimmune reaction. In rodent models of diabetes, streptozotocin...

Alkylpurine–DNA–N-Glycosylase Knockout Mice Show Increased Susceptibility to Induction of Mutations by Methyl Methanesulfonate

Elder, Rhoderick H., Jansen, Jacob G., Weeks, Robert J., Willington, Mark A., Deans, Bryan, Watson, Amanda J., ...

Alkylpurine-DNA-N-glycosylase (APNG) null mice have been generated by homologous recombination in embryonic stem cells. The null status of the animals was confirmed at the mRNA level by reverse...

Inhibition of O6-methylguanine-DNA methyltransferase by an alkyltransferase-like protein from Escherichia coli

Pearson, Steven J., Ferguson, Jennifer, Santibanez-Koref, Mauro, Margison, Geoffrey P.

The alkyltransferase-like (ATL) proteins contain primary sequence motifs resembling those found in DNA repair O6-alkylguanine-DNA alkyltransferase proteins. However, in the putative active site of...

Are There Low-Penetrance TP53 Alleles? Evidence from Childhood Adrenocortical Tumors

Varley, Jennifer M., McGown, Gail, Thorncroft, Mary, James, Louise A., Margison, Geoffrey P., Forster, Gill, ...

We have analyzed a panel of 14 cases of childhood adrenocortical tumors unselected for family history and have identified germline TP53 mutations in >80%, making this the highest known incidence of a...

Novel synthesis of O6-alkylguanine containing oligodeoxyribonucleotides as substrates for the human DNA repair protein, O6-methylguanine DNA methyltransferase (MGMT)

Shibata, Takayuki, Glynn, Nicola, McMurry, T. Brian H., McElhinney, R. Stanley, Margison, Geoffrey P., Williams, David M.

The human DNA repair protein O6-methylguanine DNA methyltransferase (MGMT) dealkylates mutagenic O6-alkylguanine lesions within DNA in an irreversible reaction which results in inactivation of the...

A novel DNA damage recognition protein in Schizosaccharomyces pombe

Pearson, Steven J., Wharton, Stephen, Watson, Amanda J., Begum, Ghazala, Butt, Amna, Glynn, Nicola, ...

Toxic and mutagenic O6-alkylguanine adducts in DNA are repaired by O6-alkylguanine-DNA alkyltransferases (MGMT) by transfer of the alkyl group to a cysteine residue in the active site. Comparisons in...

Multicistronic lentiviral vectors containing the FMDV 2A cleavage factor demonstrate robust expression of encoded genes at limiting MOI

Chinnasamy, Dhanalakshmi, Milsom, Michael D, Shaffer, James, Neuenfeldt, James, Shaaban, Aimen F, Margison, Geoffrey P, ...