Adaptive response
Encyclopedia
The adaptive response is a form of direct DNA repair
in E. coli that is initiated against alkylation
, particularly methylation
, of guanine
or thymine
nucleotide
s or phosphate
groups on the sugar-phosphate backbone of DNA
. Under sustained exposure to low-level treatment with alkylating mutagen
s, E. coli can adapt to the presence of the mutagen, rendering subsequent treatment with high doses of the same agent less effective.
The adaptive response is mediated by the ada
protein, which covalently transfers alkyl groups from the damaged DNA to one of its two cysteine
residues
, rendering the protein enzymatically dead. It is thus a "suicide" protein that reacts stoichiometrically rather than catalytically
. Methylated ada acts as a transcription factor
to initiate the adaptive response, promoting the expression
of related genes such as alkA, alkB
, aidB, and ada itself. The alkA gene product is a glycosylase, the aidB product is a flavin-containing protein, and alkB is an iron
-dependent oxidoreductase
; all are involved in further DNA repairs of alkylation damage.
DNA repair
DNA repair refers to a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as UV light and radiation can cause DNA damage, resulting in as many as 1...
in E. coli that is initiated against alkylation
Alkylation
Alkylation is the transfer of an alkyl group from one molecule to another. The alkyl group may be transferred as an alkyl carbocation, a free radical, a carbanion or a carbene . Alkylating agents are widely used in chemistry because the alkyl group is probably the most common group encountered in...
, particularly methylation
Methylation
In the chemical sciences, methylation denotes the addition of a methyl group to a substrate or the substitution of an atom or group by a methyl group. Methylation is a form of alkylation with, to be specific, a methyl group, rather than a larger carbon chain, replacing a hydrogen atom...
, of guanine
Guanine
Guanine is one of the four main nucleobases found in the nucleic acids DNA and RNA, the others being adenine, cytosine, and thymine . In DNA, guanine is paired with cytosine. With the formula C5H5N5O, guanine is a derivative of purine, consisting of a fused pyrimidine-imidazole ring system with...
or thymine
Thymine
Thymine is one of the four nucleobases in the nucleic acid of DNA that are represented by the letters G–C–A–T. The others are adenine, guanine, and cytosine. Thymine is also known as 5-methyluracil, a pyrimidine nucleobase. As the name suggests, thymine may be derived by methylation of uracil at...
nucleotide
Nucleotide
Nucleotides are molecules that, when joined together, make up the structural units of RNA and DNA. In addition, nucleotides participate in cellular signaling , and are incorporated into important cofactors of enzymatic reactions...
s or phosphate
Phosphate
A phosphate, an inorganic chemical, is a salt of phosphoric acid. In organic chemistry, a phosphate, or organophosphate, is an ester of phosphoric acid. Organic phosphates are important in biochemistry and biogeochemistry or ecology. Inorganic phosphates are mined to obtain phosphorus for use in...
groups on the sugar-phosphate backbone of DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
. Under sustained exposure to low-level treatment with alkylating mutagen
Mutagen
In genetics, a mutagen is a physical or chemical agent that changes the genetic material, usually DNA, of an organism and thus increases the frequency of mutations above the natural background level. As many mutations cause cancer, mutagens are therefore also likely to be carcinogens...
s, E. coli can adapt to the presence of the mutagen, rendering subsequent treatment with high doses of the same agent less effective.
The adaptive response is mediated by the ada
Ada (protein)
Ada is an enzyme induced by treatment of bacterial cells with alkylating agents that mainly cause methylation damage. This phenomenon is called the adaptive response and hence the name. Ada is also called as O6 alkyl guanine transferase I . Ada transfers the alkyl group from DNA bases and...
protein, which covalently transfers alkyl groups from the damaged DNA to one of its two cysteine
Cysteine
Cysteine is an α-amino acid with the chemical formula HO2CCHCH2SH. It is a non-essential amino acid, which means that it is biosynthesized in humans. Its codons are UGU and UGC. The side chain on cysteine is thiol, which is polar and thus cysteine is usually classified as a hydrophilic amino acid...
residues
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
, rendering the protein enzymatically dead. It is thus a "suicide" protein that reacts stoichiometrically rather than catalytically
Catalysis
Catalysis is the change in rate of a chemical reaction due to the participation of a substance called a catalyst. Unlike other reagents that participate in the chemical reaction, a catalyst is not consumed by the reaction itself. A catalyst may participate in multiple chemical transformations....
. Methylated ada acts as a transcription factor
Transcription factor
In molecular biology and genetics, a transcription factor is a protein that binds to specific DNA sequences, thereby controlling the flow of genetic information from DNA to mRNA...
to initiate the adaptive response, promoting the expression
Gene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...
of related genes such as alkA, alkB
AlkB
AlkB protein is a protein induced during an adaptive response and is involved in the direct reversal of alkylation damage [1]. AlkB specifically removes alkylation damage to single stranded DNA caused by SN2 type of chemical agents [2]. It efficiently removes methyl groups from 1-methyl...
, aidB, and ada itself. The alkA gene product is a glycosylase, the aidB product is a flavin-containing protein, and alkB is an iron
Iron
Iron is a chemical element with the symbol Fe and atomic number 26. It is a metal in the first transition series. It is the most common element forming the planet Earth as a whole, forming much of Earth's outer and inner core. It is the fourth most common element in the Earth's crust...
-dependent oxidoreductase
Oxidoreductase
In biochemistry, an oxidoreductase is an enzyme that catalyzes the transfer of electrons from one molecule to another...
; all are involved in further DNA repairs of alkylation damage.