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dc.contributor.authorMargison, Geoffrey P
dc.contributor.authorButt, Amna
dc.contributor.authorPearson, Steven J
dc.contributor.authorWharton, Stephen
dc.contributor.authorWatson, Amanda J
dc.contributor.authorMarriott, Andrew S
dc.contributor.authorCaetano, Cátia M P F
dc.contributor.authorHollins, Jeffrey J
dc.contributor.authorRukazenkova, Natalia
dc.contributor.authorBegum, Ghazala
dc.contributor.authorSantibanez-Koref, Mauro F
dc.date.accessioned2009-06-12T14:39:14Z
dc.date.available2009-06-12T14:39:14Z
dc.date.issued2007-08-01
dc.identifier.citationAlkyltransferase-like proteins. 2007, 6 (8):1222-8 DNA Repairen
dc.identifier.issn1568-7864
dc.identifier.pmid17500045
dc.identifier.doi10.1016/j.dnarep.2007.03.014
dc.identifier.urihttp://hdl.handle.net/10541/70330
dc.description.abstractRecent in silico analysis has revealed the presence of a group of proteins in pro and lower eukaryotes, but not in Man, that show extensive amino acid sequence similarity to known O(6)-alkylguanine-DNA alkyltransferases, but where the cysteine at the putative active site is replaced by another residue, usually tryptophan. Here we review recent work on these proteins, which we designate as alkyltransferase-like (ATL) proteins, and consider their mechanism of action and role in protecting the host organisms against the biological effects of O(6)-alkylating agents, and their evolution. ATL proteins from Escherichia coli (eAtl, transcribed from the ybaz open reading frame) and Schizosaccharomyces pombe (Atl1) are able to bind to a range of O(6)-alkylguanine residues in DNA and to reversibly inhibit the action of the human alkyltransferase (MGMT) upon these substrates. Isolated proteins were not able to remove the methyl group in O(6)-methylguanine-containing DNA or oligonucleotides, neither did they display glycosylase or endonuclease activity. S. pombe does not contain a functional alkyltransferase and atl1 inactivation sensitises this organism to a variety of alkylating agents, suggesting that Atl1 acts by binding to O(6)-alkylguanine lesions and signalling them for processing by other DNA repair pathways. Currently we cannot exclude the possibility that ATL proteins arose through independent mutation of the alkyltransferase gene in different organisms. However, analyses of the proteins from E. coli and S. pombe, are consistent with a common function.
dc.language.isoenen
dc.subjectTumour Suppressor Proteinsen
dc.subject.meshAlkyl and Aryl Transferases
dc.subject.meshAlkylating Agents
dc.subject.meshAmino Acid Sequence
dc.subject.meshAnimals
dc.subject.meshDNA Modification Methylases
dc.subject.meshDNA Repair
dc.subject.meshDNA Repair Enzymes
dc.subject.meshEvolution, Molecular
dc.subject.meshGene Deletion
dc.subject.meshGenes, Fungal
dc.subject.meshHumans
dc.subject.meshMolecular Sequence Data
dc.subject.meshO(6)-Methylguanine-DNA Methyltransferase
dc.subject.meshPhylogeny
dc.subject.meshSequence Homology, Amino Acid
dc.subject.meshSpecies Specificity
dc.subject.meshTumor Suppressor Proteins
dc.titleAlkyltransferase-like proteins.en
dc.typeArticleen
dc.contributor.departmentCancer Research-UK Carcinogenesis Group, Paterson Institute for Cancer Research, University of Manchester, Manchester M20 4BX, United Kingdom. gmargison@picr.man.ac.uken
dc.identifier.journalDNA Repairen
html.description.abstractRecent in silico analysis has revealed the presence of a group of proteins in pro and lower eukaryotes, but not in Man, that show extensive amino acid sequence similarity to known O(6)-alkylguanine-DNA alkyltransferases, but where the cysteine at the putative active site is replaced by another residue, usually tryptophan. Here we review recent work on these proteins, which we designate as alkyltransferase-like (ATL) proteins, and consider their mechanism of action and role in protecting the host organisms against the biological effects of O(6)-alkylating agents, and their evolution. ATL proteins from Escherichia coli (eAtl, transcribed from the ybaz open reading frame) and Schizosaccharomyces pombe (Atl1) are able to bind to a range of O(6)-alkylguanine residues in DNA and to reversibly inhibit the action of the human alkyltransferase (MGMT) upon these substrates. Isolated proteins were not able to remove the methyl group in O(6)-methylguanine-containing DNA or oligonucleotides, neither did they display glycosylase or endonuclease activity. S. pombe does not contain a functional alkyltransferase and atl1 inactivation sensitises this organism to a variety of alkylating agents, suggesting that Atl1 acts by binding to O(6)-alkylguanine lesions and signalling them for processing by other DNA repair pathways. Currently we cannot exclude the possibility that ATL proteins arose through independent mutation of the alkyltransferase gene in different organisms. However, analyses of the proteins from E. coli and S. pombe, are consistent with a common function.


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