Depurination
Encyclopedia
In molecular genetics
, depurination is an alteration of DNA
in which the purine
base (adenine
or guanine
) is removed from the deoxyribose
sugar by hydrolysis
of the beta-N-glycosidic link
between them. After depurination, an apurinic site is formed where the sugar phosphate backbone remains and the sugar ring has a hydroxyl
(-OH) group in the place of the purine. Studies estimate that as many as 5,000 purines are lost this way each day in a typical human cell. One of the main causes of depurination is the presence of endogenous metabolites in cell undergoing chemical reactions. Depurinated bases in double-stranded DNA are efficiently repaired by portions of the base excision repair
(BER) pathway. Depurinated bases in single-stranded DNA undergoing replication
can lead to mutations, because in the absence of information from the complementary strand, BER can add an incorrect base at the apurinic site, resulting in either a transition
or transversion
mutation. Loss of pyrimidine
bases (Cytosine
and Thymine
) occurs by a similar mechanism, but at a substantially lower rate.
Hydrolytic depurination is one of the principal forms of damage to ancient DNA
in fossil or subfossil material, since the base remains unrepaired. This results in both loss of information (the base sequence), and difficulties in recovery and in vitro replication of the damaged molecule by the polymerase chain reaction
.
via the 8N-nitrogen (see the structure of a purine
). Furthermore, the anomeric carbon is especially reactive towards nucleophilic substitution
(effectively making the carbon-oxygen bond shorter, stronger and more polar, while making the carbon-purine bond longer and weaker). This makes the bond especially susceptible to hydrolysis.
Molecular genetics
Molecular genetics is the field of biology and genetics that studies the structure and function of genes at a molecular level. The field studies how the genes are transferred from generation to generation. Molecular genetics employs the methods of genetics and molecular biology...
, depurination is an alteration 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...
in which the purine
Purine
A purine is a heterocyclic aromatic organic compound, consisting of a pyrimidine ring fused to an imidazole ring. Purines, including substituted purines and their tautomers, are the most widely distributed kind of nitrogen-containing heterocycle in nature....
base (adenine
Adenine
Adenine is a nucleobase with a variety of roles in biochemistry including cellular respiration, in the form of both the energy-rich adenosine triphosphate and the cofactors nicotinamide adenine dinucleotide and flavin adenine dinucleotide , and protein synthesis, as a chemical component of DNA...
or 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...
) is removed from the deoxyribose
Deoxyribose
Deoxyribose, more, precisely 2-deoxyribose, is a monosaccharide with idealized formula H---3-H. Its name indicates that it is a deoxy sugar, meaning that it is derived from the sugar ribose by loss of an oxygen atom...
sugar by hydrolysis
Hydrolysis
Hydrolysis is a chemical reaction during which molecules of water are split into hydrogen cations and hydroxide anions in the process of a chemical mechanism. It is the type of reaction that is used to break down certain polymers, especially those made by condensation polymerization...
of the beta-N-glycosidic link
Glycosidic bond
In chemistry, a glycosidic bond is a type of covalent bond that joins a carbohydrate molecule to another group, which may or may not be another carbohydrate....
between them. After depurination, an apurinic site is formed where the sugar phosphate backbone remains and the sugar ring has a hydroxyl
Hydroxyl
A hydroxyl is a chemical group containing an oxygen atom covalently bonded with a hydrogen atom. In inorganic chemistry, the hydroxyl group is known as the hydroxide ion, and scientists and reference works generally use these different terms though they refer to the same chemical structure in...
(-OH) group in the place of the purine. Studies estimate that as many as 5,000 purines are lost this way each day in a typical human cell. One of the main causes of depurination is the presence of endogenous metabolites in cell undergoing chemical reactions. Depurinated bases in double-stranded DNA are efficiently repaired by portions of the base excision repair
Base excision repair
In biochemistry and genetics, base excision repair is a cellular mechanism that repairs damaged DNA throughout the cell cycle. It is responsible primarily for removing small, non-helix-distorting base lesions from the genome. The related nucleotide excision repair pathway repairs bulky...
(BER) pathway. Depurinated bases in single-stranded DNA undergoing replication
DNA replication
DNA replication is a biological process that occurs in all living organisms and copies their DNA; it is the basis for biological inheritance. The process starts with one double-stranded DNA molecule and produces two identical copies of the molecule...
can lead to mutations, because in the absence of information from the complementary strand, BER can add an incorrect base at the apurinic site, resulting in either a transition
Transition (genetics)
In genetics, a transition is a point mutation that changes a purine nucleotide to another purine or a pyrimidine nucleotide to another pyrimidine . Approximately two out of three single nucleotide polymorphisms are transitions....
or transversion
Transversion
In molecular biology, transversion refers to the substitution of a purine for a pyrimidine or vice versa. It can only be reverted by a spontaneous reversion. Because this type of mutation changes the chemical structure dramatically, the consequences of this change tend to be more drastic than those...
mutation. Loss of pyrimidine
Pyrimidine
Pyrimidine is a heterocyclic aromatic organic compound similar to benzene and pyridine, containing two nitrogen atoms at positions 1 and 3 of the six-member ring...
bases (Cytosine
Cytosine
Cytosine is one of the four main bases found in DNA and RNA, along with adenine, guanine, and thymine . It is a pyrimidine derivative, with a heterocyclic aromatic ring and two substituents attached . The nucleoside of cytosine is cytidine...
and 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...
) occurs by a similar mechanism, but at a substantially lower rate.
Hydrolytic depurination is one of the principal forms of damage to ancient DNA
Ancient DNA
Ancient DNA is DNA isolated from ancient specimens. It can be also loosely described as any DNA recovered from biological samples that have not been preserved specifically for later DNA analyses...
in fossil or subfossil material, since the base remains unrepaired. This results in both loss of information (the base sequence), and difficulties in recovery and in vitro replication of the damaged molecule by the polymerase chain reaction
Polymerase chain reaction
The polymerase chain reaction is a scientific technique in molecular biology to amplify a single or a few copies of a piece of DNA across several orders of magnitude, generating thousands to millions of copies of a particular DNA sequence....
.
Chemistry of the reaction
Depurination is not uncommon because purine is a good leaving groupLeaving group
In chemistry, a leaving group is a molecular fragment that departs with a pair of electrons in heterolytic bond cleavage. Leaving groups can be anions or neutral molecules. Common anionic leaving groups are halides such as Cl−, Br−, and I−, and sulfonate esters, such as para-toluenesulfonate...
via the 8N-nitrogen (see the structure of a purine
Purine
A purine is a heterocyclic aromatic organic compound, consisting of a pyrimidine ring fused to an imidazole ring. Purines, including substituted purines and their tautomers, are the most widely distributed kind of nitrogen-containing heterocycle in nature....
). Furthermore, the anomeric carbon is especially reactive towards nucleophilic substitution
Nucleophilic substitution
In organic and inorganic chemistry, nucleophilic substitution is a fundamental class of reactions in which an electron nucleophile selectively bonds with or attacks the positive or partially positive charge of an atom or a group of atoms called the leaving group; the positive or partially positive...
(effectively making the carbon-oxygen bond shorter, stronger and more polar, while making the carbon-purine bond longer and weaker). This makes the bond especially susceptible to hydrolysis.