AuthorsMargison, Geoffrey P
Pearson, Steven J
Watson, Amanda J
Marriott, Andrew S
Caetano, Cátia M P F
Hollins, Jeffrey J
Santibanez-Koref, Mauro F
AffiliationCancer Research-UK Carcinogenesis Group, Paterson Institute for Cancer Research, University of Manchester, Manchester M20 4BX, United Kingdom. email@example.com
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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.
CitationAlkyltransferase-like proteins. 2007, 6 (8):1222-8 DNA Repair
- A novel DNA damage recognition protein in Schizosaccharomyces pombe.
- Authors: Pearson SJ, Wharton S, Watson AJ, Begum G, Butt A, Glynn N, Williams DM, Shibata T, Santibáñez-Koref MF, Margison GP
- Issue date: 2006
- Inhibition of O6-methylguanine-DNA methyltransferase by an alkyltransferase-like protein from Escherichia coli.
- Authors: Pearson SJ, Ferguson J, Santibanez-Koref M, Margison GP
- Issue date: 2005
- The bacterial alkyltransferase-like (eATL) protein protects mammalian cells against methylating agent-induced toxicity.
- Authors: Tomaszowski KH, Aasland D, Margison GP, Williams E, Pinder SI, Modesti M, Fuchs RP, Kaina B
- Issue date: 2015 Apr
- MGMT: key node in the battle against genotoxicity, carcinogenicity and apoptosis induced by alkylating agents.
- Authors: Kaina B, Christmann M, Naumann S, Roos WP
- Issue date: 2007 Aug 1
- DNA binding, nucleotide flipping, and the helix-turn-helix motif in base repair by O6-alkylguanine-DNA alkyltransferase and its implications for cancer chemotherapy.
- Authors: Tubbs JL, Pegg AE, Tainer JA
- Issue date: 2007 Aug 1