Disease relevance of alkB

• Escherichia coli alkB mutants are very sensitive to DNA methylating agents [1].
• Here, we report that reactivation of methylmethanesulfonate (MMS)-treated single-stranded DNA phages, M13, f1, and G4, was decreased dramatically in alkB mutants [1].
• We have identified and sequenced the Pseudomonas OCT plasmid-encoded alkane hydroxylase gene (alkB) and its promoter [2].
• An alkB gene homolog is differentially transcribed during the Caulobacter crescentus cell cycle [3].
• The two genes allow an alkane hydroxylase-negative mutant of Acinetobacter sp. ADP1 and an Escherichia coli recombinant containing all P. oleovorans alk genes except alkB, respectively, to grow on n-alkanes, showing that the cloned genes do indeed encode alkane hydroxylases [4].

High impact information on alkB

• Consistent with this theory, stationary phase alkB cells were less MMS sensitive than rapidly growing cells [1].
• These data show that alkB mutants have a marked defect in processing methylation damage in single-stranded DNA [1].
• For nearly two decades, we have known that the Escherichia coli alkB gene product protects against cell killing by S(N)2-alkylating agents, probably through DNA repair [5].
• Mutagenesis, genotoxicity, and repair of 1-methyladenine, 3-alkylcytosines, 1-methylguanine, and 3-methylthymine in alkB Escherichia coli [6].
• Here, we identify two human AlkB homologs, ABH2 and ABH3, by sequence and fold similarity, functional assays, and complementation of the E. coli alkB mutant phenotype [7].

Chemical compound and disease context of alkB

• Our data show that MNNG induction of UVM is independent of ada, alkA and alkB genes and define UVM as an inducible mutagenic phenomenon distinct from the E. coli adaptive and SOS responses [8].
• A new gene (alkB) of Escherichia coli that controls sensitivity to methyl methane sulfonate [9].
• By DNA blot hybridization analysis we show that the alkylation-sensitive E. coli mutant BS23 [Sedgwick, B. & Lindahl, T. (1982) J. Mol. Biol. 154, 169-175] is a deletion mutant lacking the entire ada-alkB operon [10].
• When the alkB gene of Escherichia coli that controls sensitivity of bacteria to methyl methanesulfonate was placed under the control of the lac regulatory region on a multicopy plasmid, the gene product, AlkB protein, was overproduced [11].
• The alkB gene is one of a group of alkylation-inducible genes in Escherichia coli, and its product protects cells from SN2-type alkylating agents such as methyl methanesulfonate (MMS) [12].

Biological context of alkB

• Its phenotype was different from that of ada, since the alkB mutant exhibited a normal adaptive response to N-methyl-N'-nitro-N-nitrosoguanidine [9].
• Using methods of in vitro recombination we constructed hybrid plasmids that can suppress the increased methylmethane sulfonate sensitivity caused by alkB mutation [13].
• Introduction of a small deletion into the alkB region of the bacterial chromosome resulted in inactivation of both the alkB and ada genes, thereby suggesting that the two genes are adjacent on the E. coli chromosome [13].
• We have subcloned it into the pSV2 mammalian expression vector to yield pSV2ada-alkB, and this plasmid has been introduced into Mer- HeLa S3 cells, which are extremely sensitive to killing and induction of sister chromatid exchange by alkylating agents [14].
• An amino-terminal sequence and total amino acid composition of the purified AlkB protein were in accord with the amino acid sequence deduced from the nucleotide sequence of the alkB gene, determined by the phage M13 dideoxy method [11].

Anatomical context of alkB

• The Pseudomonas oleovorans alkB gene is expressed in alk+ Escherichia coli W3110 to 10 to 15% of the total cell protein, which is exceptional for a (foreign) cytoplasmic membrane protein [15].

Associations of alkB with chemical compounds

• Under aerobic conditions in the absence of alkylating agents aidB, but not alkA or alkB, was induced by an acidification of cytoplasm or by treatment with the sulfhydryl reagent N-ethylmaleimide [16].
• Furthermore, we found that alkS is responsible for activation of expression of the alkBAC operon since it is required for the induction of the alkB gene product alkane hydroxylase [17].
• We constructed hybrid plasmids carrying an alkB'-lacZ' fusion, with or without the ada control region, and investigated expression of the alkB gene in response to the alkylating agent [11].
• When hABH was expressed in E.coli alkB mutant cells partial rescue of the cells from MMS-induced cell death occurred [18].
• Also, alkB mutants were not sensitive to MeOSO2-(CH2)2-Lex, a compound that alkylates the minor groove of DNA generating primarily 3-methyladenine [19].

Other interactions of alkB

• Another mutation was found near nalA, and the gene responsible was named alkB [9].

Analytical, diagnostic and therapeutic context of alkB

• Molecular cloning and characterization of the alkB gene of Escherichia coli [13].

References