Table of Contents
What does oxoG pair with?
8-oxoG can pair with both cytosine and adenine during DNA replication, causing a G:C to T:A transversion after replication  .
How is 8-oxoguanine formed?
8-oxoguanine (8-oxoG) is formed by the oxidation of a guanine base in DNA (Fig. 10.4). It is considered to be one of the major endogenous mutagens contributing broadly to spontaneous cell transformation. Its frequent miss-pairing with adenine during replication increases the number of GC TA transversion mutations.
What mutation will 8-oxoguanine lead to?
8-oxoG is one of the candidate molecules for causing germline mutation, because it is endogenously generated by reactive oxygen species (ROS) derived from cellular respiration, constitutively exists in DNA5 and is known to cause G to T and A to C transversion mutations by the ability to pair with A as well as C during …
What happens to DNA when guanine is modified to 8-oxoguanine?
8-Oxoguanine, a major oxidized base lesion formed by reactive oxygen species, causes G to T transversion mutations or leads to cell death in mammals if it accumulates in DNA. 8-Oxoguanine can originate as 8-oxo-dGTP, formed in the nucleotide pool, or by direct oxidation of the DNA guanine base.
What is oxidative stress in simple terms?
Oxidative stress is an imbalance of free radicals and antioxidants in the body, which can lead to cell and tissue damage. Oxidative stress occurs naturally and plays a role in the aging process.
What is an Apurinic site?
In biochemistry and molecular genetics, an AP site (apurinic/apyrimidinic site), also known as an abasic site, is a location in DNA (also in RNA but much less likely) that has neither a purine nor a pyrimidine base, either spontaneously or due to DNA damage.
What is cytosine deamination?
Cytosine Deamination. When the exocyclic amino group of cytosine is removed by hydrolytic deamination, catalyzed by the AID/APOBEC family of enzymes, a cytosine analog is changed into a uracil analog. Deamination is important in immune-pathogen interactions and may play a role in active DNA demethylation.
How is 8 Oxoguanine repair?
Restriction analysis of the repair incorporation in the vicinity of the lesion indicated that up to 75% of the 8-oxoguanine was repaired via the single nucleotide replacement mechanism in both human and mouse cell extracts. Approximately 25% of the 8-oxoguanine lesions were repaired by the long patch repair pathway.
What does o6 Methylguanine pair with?
6-O-Methylguanine is a derivative of the nucleobase guanine in which a methyl group is attached to the oxygen atom. It base-pairs to thymine rather than cytosine, causing a G:C to A:T transition in DNA.
What mutation will occur as a result of DNA replication in the presence of 8 oxoG?
to T transversion During the replication of DNA that contains 8-oxo-dG, adenine is most often incorporated across from the lesion. Following replication, the 8-oxo-dG is excised during the repair process and a thymine is incorporated in its place. Thus, 8-oxo-dG mutations typically result in a G to T transversion.
Which of the following nucleotides is 8 oxo guanine able to form base pairs with?
adenine In contrast, the mutagenic syn-8-oxoG conformation is able to base pair with adenine through its Hoogsteen edge. Kinetic studies have shown that DNA polymerases insert adenine opposite 8-oxoG frequently and with enhanced catalytic efficiency when compared with guanine (4).
Why is guanine easily oxidized?
Guanine has the lowest redox potential of the four DNA bases  and is therefore the most easily oxidized.
What is guanine used for?
In the cosmetics industry, crystalline guanine is used as an additive to various products (e.g., shampoos), where it provides a pearly iridescent effect. It is also used in metallic paints and simulated pearls and plastics. It provides shimmering luster to eye shadow and nail polish.
What is the product by mutation by oxidation of DNA?
When DNA undergoes oxidative damage, two of the most common damages change guanine to 8-hydroxyguanine or to 2,6-diamino-4-hydroxy-5-formamidopyrimidine.
What is another name for thymine?
Thymine is also known as 5-methyluracil, a pyrimidine nucleobase.
How do you get rid of free radicals in your body?
Although there are several enzyme systems within the body that disarm free radicals, the principal antioxidants are vitamin E, beta-carotene, vitamin C, and selenium. When these antioxidants neutralize free radicals by donating an electron particle they are left with a small problem.
How does oxidative DNA damage occur?
Mechanisms of oxidative damage to DNA bases. Of the reactive oxygen species, the highly reactive hydroxyl radical (OH) reacts with DNA by addition to double bonds of DNA bases and by abstraction of an H atom from the methyl group of thymine and each of the C-H bonds of 2-deoxyribose (2).
What vitamins are good for oxidative stress?
Vitamin C, vitamin E, and beta-carotene, often referred to as antioxidant vitamins, have been suggested to limit oxidative damage in humans, thereby lowering the risk of certain chronic diseases.
How does Abasic or Apurinic sites cause DNA damage?
Apurinic/apyrimidinic (AP) sites are one of the most frequent spontaneous lesions in DNA. They are potentially mutagenic and lethal lesions that can block DNA replication and transcription. … AP sites can stall DNA replication forks, as well as they block in vitro DNA synthesis by DNA polymerase delta.
How are Apurinic sites made?
Apurinic/apyrimidinic (AP) sites are constantly formed in cellular DNA due to instability of the glycosidic bond, particularly at purines and various oxidized, alkylated, or otherwise damaged nucleobases. AP sites are also generated by DNA glycosylases that initiate DNA base excision repair.
What causes Depurination?
In cells, one of the main causes of depurination is the presence of endogenous metabolites undergoing chemical reactions. … Hydrolytic depurination is one of the principal forms of damage to ancient DNA in fossil or subfossil material, since the base remains unrepaired.
What is protein deamination?
Typically in humans, deamination occurs when an excess in protein is consumed, resulting in the removal of an amine group, which is then converted into ammonia and expelled via urination. This deamination process allows the body to convert excess amino acids into usable by-products.
What is liver deamination?
Deamination is the removal of an amino group from a molecule. Amino group is converted into ammonia while the amino acid itself converts into its corresponding keto acid. … In the human body, deamination takes place primarily in the liver, however it is also deaminated in the kidney.
What is Transamination and deamination?
Definition. Transamination refers to the transfer of an amino group from one molecule to another, especially from an amino acid to a keto acid, while deamination refers to the removal of an amino group from an amino acid or other compounds.
Which DNA repair pathway is implicated in Hnpcc causation?
Many cases of HNPCC syndrome result from autosomal dominant genetic mutations in one of four DNA mismatch repair (MMR) genes. Approximately one in 500 members of the general population carries a pathogenic mutation in an MMR gene, and the most common genetic predisposition to cancer overall is to HNPCC.
What is oxo G?
Among all nucleobases, guanine is the most susceptible to oxidation by ROS7 resulting in the generation of 8-oxoguanine (8-oxoG). 8-oxoG is the major oxidised base in both nucleotide pools and polymerised DNA or RNA8 , 9. … 8-oxoG can pair with adenine as well as cytosine, thereby causing G to T transversion mutations14.
Which pathway is responsible for repairing most bulky adducts?
Nucleotide Excision Repair (NER)NER is the most versatile repair pathway in the cell and the primary mechanism for the removal of chemical carcinogen-induced bulky DNA adducts that significantly distort the DNA helix structure [64, 107, 110, 111]. The molecular mechanism of NER is now well understood.
What does O6 Methylguanine do?
O6-Methylguanine methyltransferase (MGMT) is a dealkylating enzyme that removes methyl groups from the O6 position of guanine, inducing resistance to alkylating chemotherapeutic agents .
What is O6 MeG?
O6 methylguanine methyltransferase (MGMT) is a DNA repair enzyme the activity of which results in the removal of the O6 methyl group from methylguanine. Alkylating chemotherapeutic agents such as temozolomide act to disrupt DNA replication by methylation of DNA base pairs.
How is Methylguanine repaired?
Methylating agents induce in the DNA O6-methylguanine (O6MeG) and methylations of the ring nitrogens of purines. The lesions are repaired by O6-methylguanine-DNA methyltransferase (Mgmt) and by enzymes of the base excision repair (BER) pathway, respectively.