Alkyltransferase-like proteins

Margison, Geoffrey P.; Butt, Amna; Pearson, S. J.; Wharton, Stephen; Watson, Amanda J.; Marriott, Anna; Caetano, Catia; Hollins, Jeffrey J.; Rukazenkova, Natalia; Begum, Ghazala; Santibanez‐Koref, Mauro

doi:10.1016/j.dnarep.2007.03.014

Cited by 44 publications

(36 citation statements)

References 19 publications

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“…However, different from what was observed in all the crystal structures of OGTs, in both the MtOGT and MtOGT-R37L models the active-site loop is oriented toward the exterior of the protein body (Fig. 4A), adopting a conformation that closely resembles the one displayed by the equivalent region in the structures of alkyltransferase-like proteins (ATLs) (47) in complex with alkylated DNA (48,49) (Fig. 4B).…”

Section: Figmentioning

confidence: 93%

Biochemical and Structural Studies of the Mycobacterium tuberculosis O ⁶ -Methylguanine Methyltransferase and Mutated Variants

et al. 2013

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Section: Figmentioning

confidence: 93%

Biochemical and Structural Studies of the Mycobacterium tuberculosis O ⁶ -Methylguanine Methyltransferase and Mutated Variants

et al. 2013

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“…It turns out that eATL interferes with the processing of these O 6 -alkylguanine lesions at two levels: First, it enhances NER, thus diminishing both mutagenesis and toxicity (16), and second, it inhibits the action of the MMR system on O 6 -alkylguanine:T intermediates, thus lowering toxicity at the cost of mutagenesis. Although ATL proteins are present in all three kingdoms of life, no ATL homolog in higher eukaryotes or plants has yet been found (17,18,22). One may speculate that the DNA damage binding protein complex UV-DDB (36) that recognizes lesions such as UV-induced cyclobutane dimers, AP sites (apurinic/apyrimidinic sites), and so forth may act as a functional homolog of ATL.…”

Section: Resultsmentioning

confidence: 99%

“…17), stimulates the repair by NER of O 6 -alkylguanine adducts (16). Whereas eATL binds to O 6 -alkylguanine adducts, it is devoid of any alkyltransferase activity (18,19) and thus, unlike Ada or Ogt, does not act as a repair factor per se. eATL merely promotes repair via an "enhanced NER" pathway by facilitating the recruitment of the NER factors to the O 6 -alkylguanine lesion sites that are otherwise poor substrates (16), akin to the stimulation of photoproduct excision by the binding of photolyase in the absence of light (20).…”

mentioning

confidence: 99%

Alkyltransferase-like protein (eATL) prevents mismatch repair-mediated toxicity induced by O ⁶ -alkylguanine adducts in Escherichia coli

Mazón

Philippin

Cadet

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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O 6 -alkylG adducts are highly mutagenic due to their capacity to efficiently form O 6 -alkylG:T mispairs during replication, thus triggering G→A transitions. Mutagenesis is largely prevented by repair strategies such as reversal by alkyltransferases or excision by nucleotide excision repair (NER). Moreover, methyl-directed mismatch repair (MMR) is known to trigger sensitivity to methylating agents via a mechanism that involves recognition by MutS of the O 6 -mG:T replication intermediates. We wanted to investigate the mechanism by which MMR controls the genotoxicity of environmentally relevant O 6 -alkylG adducts formed by ethylene oxide and propylene oxide. Recently, the alkyltransferase-like gene ybaZ (eATL) was shown to enhance repair of these slightly larger O 6 -alkylG adducts by NER. We analyzed the toxicity and mutagenesis induced by these O 6 -alkylG adducts using single-adducted plasmid probes. We show that the eATL gene product prevents MMR-mediated attack of the O 6 -alkylG:T replication intermediate for the larger alkyl groups but not for methyl. In vivo data are compatible with the occurrence of repeated cycles of MMR attack of the O 6 -alkylG:T intermediate. In addition, in vitro, the eATL protein efficiently prevents binding of MutS to the O 6 -alkylG:T mispairs formed by the larger alkyl groups but not by methyl. In conclusion, eATL not only enhances the efficiency of repair of these larger adducts by NER, it also shields these adducts from MMR-mediated toxicity.futile mismatch repair cycling | interference between repair pathways | nucleotide excision repair | ybaZ gene

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“…In silico analysis of genomic sequences suggests the presence of a family of AGT homologs (ATLs) with sequence similarity to the AGT catalytic domain, with the exception that the active cysteine residue is replaced by tryptophan, alanine, or other residues, all of which are not capable of nucleophilic attack (Margison et al 2003(Margison et al , 2007. ATLs tightly bind ss/ dsDNA that contain O 6 -alkyl guanine, but they display no alkyltransferase, demethylase, glycosylase, or endonuclease activity (Pearson et al 2005(Pearson et al , 2006Chen et al 2008;Morita et al 2008).…”

Section: Repair Of Alkylation Damage By Alkyltransferase-like Proteinmentioning

confidence: 99%

DNA Repair by Reversal of DNA Damage

2013

Cold Spring Harbor Perspectives in Biology

132

115

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Endogenous and exogenous factors constantly challenge cellular DNA, generating cytotoxic and/or mutagenic DNA adducts. As a result, organisms have evolved different mechanisms to defend against the deleterious effects of DNA damage. Among these diverse repair pathways, direct DNA-repair systems provide cells with simple yet efficient solutions to reverse covalent DNA adducts. In this review, we focus on recent advances in the field of direct DNA repair, namely, photolyase-, alkyltransferase-, and dioxygenase-mediated repair processes. We present specific examples to describe new findings of known enzymes and appealing discoveries of new proteins. At the end of this article, we also briefly discuss the influence of direct DNA repair on other fields of biology and its implication on the discovery of new biology. E ndogenous and environmental agents continuously threaten the genomic integrity of all living organisms. Replication of damaged DNA can lead to mutations that are tumorigenic, whereas DNA lesions that block replication or transcription can result in senescence and cell death. Therefore, cellular DNA must be promptly repaired. Well-known mechanisms include base-excision repair, nucleotide excision repair, mismatch repair, homologous recombination, and nonhomologous end joining. In addition, nature has also evolved several mechanisms in which the damage is directly reversed most often by a single repair protein without the incision of DNA backbone. Although such "direct repair" processes mediate the reversal of a relatively small set of DNA lesions, the simplicity and essentially error-free property of the direct reversal processes make them particularly attractive for a cell. Three major mechanisms of direct DNA repair have been identified to date: (i) photolyases reverse UV light-induced photolesions; (ii) O 6 -alkylguanine-DNA alkyltransferases (AGTs) reverse a set of O-alkylated DNA damage; and (iii) the AlkB family dioxygenases reverse N-alkylated base adducts (Fig. 1). This concise article intends to update knowledge since the publication of the second edition of DNA Repair and Mutagenesis (ASM) (Friedberg et al. 2006).

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Alkyltransferase-like proteins

Cited by 44 publications

References 19 publications

Biochemical and Structural Studies of the Mycobacterium tuberculosis O ⁶ -Methylguanine Methyltransferase and Mutated Variants

Biochemical and Structural Studies of the Mycobacterium tuberculosis O ⁶ -Methylguanine Methyltransferase and Mutated Variants

Alkyltransferase-like protein (eATL) prevents mismatch repair-mediated toxicity induced by O ⁶ -alkylguanine adducts in Escherichia coli

DNA Repair by Reversal of DNA Damage

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Alkyltransferase-like proteins

Cited by 44 publications

References 19 publications

Biochemical and Structural Studies of the Mycobacterium tuberculosis O 6 -Methylguanine Methyltransferase and Mutated Variants

Biochemical and Structural Studies of the Mycobacterium tuberculosis O 6 -Methylguanine Methyltransferase and Mutated Variants

Alkyltransferase-like protein (eATL) prevents mismatch repair-mediated toxicity induced by O 6 -alkylguanine adducts in Escherichia coli

DNA Repair by Reversal of DNA Damage

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Biochemical and Structural Studies of the Mycobacterium tuberculosis O ⁶ -Methylguanine Methyltransferase and Mutated Variants

Biochemical and Structural Studies of the Mycobacterium tuberculosis O ⁶ -Methylguanine Methyltransferase and Mutated Variants

Alkyltransferase-like protein (eATL) prevents mismatch repair-mediated toxicity induced by O ⁶ -alkylguanine adducts in Escherichia coli