What is depurination and deamination? Describe the repair systems that operate after depurination and deamination

Depurination and deamination are two types of spontaneous mutations that occur naturally within the DNA of cells. These are not caused by external agents but happen due to chemical instability in DNA under normal cellular conditions. Both processes can lead to mutations if not repaired in time, but cells have efficient repair mechanisms, especially the Base Excision Repair (BER) pathway, that work to correct these damages and maintain the genetic integrity of the organism.

Depurination

Depurination refers to the loss of a purine base, which is either adenine or guanine, from the DNA. This occurs when the N-glycosidic bond between the purine base and the deoxyribose sugar breaks due to hydrolysis. As a result, the base is removed but the sugar-phosphate backbone of the DNA remains intact. The site from where the purine base is lost is called an apurinic site (AP site).

If this AP site is not repaired before DNA replication, the DNA polymerase may insert an incorrect base at that position, leading to a point mutation. Depurination is very common in cells and can happen thousands of times per day.

Deamination

Deamination is the removal of an amino group (-NH₂) from a nitrogenous base in DNA. This changes the chemical identity of the base and can alter its base-pairing properties. The most common form of deamination is:
  • Cytosine to Uracil: Cytosine, when deaminated, becomes uracil. Since uracil pairs with adenine, this can lead to a C-G to T-A transition mutation during replication.
Other forms include:
  • Adenine to Hypoxanthine: Pairs with cytosine instead of thymine.
  • Guanine to Xanthine: Has altered pairing behavior
Deamination is also spontaneous but can be increased by chemicals like nitrous acid.

Repair Systems for Depurination and Deamination

The major pathway that repairs damage caused by both depurination and deamination is the Base Excision Repair (BER) mechanism. It is highly specific and accurate in correcting small, non-bulky base lesions.

Steps of Base Excision Repair:

1. Recognition of Damage

The first step in the BER pathway is the recognition of abnormal or missing bases.
  • In deamination, the DNA still contains a base, but that base has been chemically changed. For example:
    • Cytosine becomes uracil.
  • Adenine becomes hypoxanthine. These altered bases are recognized by DNA glycosylase enzymes that are specific to each type of damage.
  • In depurination, there is no base left at the damaged site. This creates an apurinic site (AP site), which is directly recognized by the next enzyme in the pathway.

2. Removal of Damaged or Abnormal Base

  • In deamination, the specific DNA glycosylase removes the damaged base by cleaving the N-glycosidic bond between the base and the sugar. This leaves behind an AP site. Example:
    • Uracil-DNA glycosylase removes uracil formed from cytosine deamination.
  • Other glycosylases remove hypoxanthine or xanthine.
  • In depurination, since the purine base is already missing, this step is skipped. The AP site is already formed.

3. Cutting the DNA Backbone

Once the AP site is formed, the enzyme AP endonuclease cuts the DNA backbone at that site. This creates a small gap in the DNA strand, preparing it for insertion of the correct nucleotide.

4. Removal of Sugar Residue

After the cut, the sugar (deoxyribose) that was holding the base is still present. This sugar is removed by phosphodiesterase or a similar enzyme, leaving a clean gap in the DNA strand.

5. Synthesis of New Base

The gap is now filled with the correct base by DNA polymerase. It uses the complementary strand as a template to insert the right nucleotide that was originally present before the damage.

6. Sealing the DNA Strand

Finally, the enzyme DNA ligase seals the small break in the sugar-phosphate backbone. This completes the repair process and restores the strength and continuity of the DNA strand.




Comments

  1. AnonymousJuly 29, 2025 at 2:57 PM

    The good one 👍short and significant information and a simple word .

    ReplyDelete

Post a Comment

Popular posts from this blog

What is gene therapy and how does it work to treat genetic disorders?

Gene therapy is an advanced medical approach designed to treat or potentially  cure genetic disorders  by modifying or replacing faulty genes within a patient's cells. Genetic disorders arise due to mutations or defects in DNA, leading to the production of abnormal, insufficient or missing proteins necessary for normal bodily functions. Unlike conventional treatments that manage symptoms, gene therapy targets the  root cause  of genetic diseases, making it a highly promising and potentially curative strategy. It is particularly effective for monogenic disorders (caused by mutations in a single gene), but ongoing research is exploring its application in more complex, polygenic conditions. The foundation of gene therapy was laid by  William French Anderson, Michael Blaese and Kenneth Culver,  who conducted the first successful gene therapy trial in  1990  to treat  severe combined immunodeficiency (SCID)  caused by  ADA deficiency. ...
Read more

What are epigenetic modifications? Give examples

Epigenetic modifications are heritable and reversible changes in gene expression that occur  without altering the DNA sequence  itself. These changes play a major role in how genes are  turned on or off  in different cells and at different times. Epigenetics helps explain how the same DNA sequence can produce different types of cells like skin cells, nerve cells and liver cells in the same organism. These modifications are very important during development, cellular differentiation, X-chromosome inactivation in females, genomic imprinting, aging and in many diseases such as cancer. There are the following three main types of epigenetic modifications: 1. DNA Methylation This is the most studied and well-understood form of epigenetic modification. In this process, a methyl group (–CH₃) is added to the cytosine base in DNA, mainly at CpG dinucleotides. These CpG regions are often found in clusters called CpG islands, which are located near  gene promoters.  DN...
Read more

What are non-coding genes? Give examples

Non-coding genes are segments of DNA that do not code for any protein but still play very important roles in the cell. These genes are transcribed into functional RNA molecules instead of mRNA. These RNAs do not get translated into proteins but perform regulatory, structural, or catalytic roles directly as RNA. Non-coding genes are a major part of the eukaryotic genome and help in many cellular processes such as gene regulation, RNA processing and maintaining genome stability. Many people think that only protein-coding genes matter, but non-coding genes also play a crucial role in regulating cellular activities. They help control when and how genes are turned on or off, assist in processing other RNAs and participate in building cell machinery like ribosomes and spliceosomes. There are several important types of non-coding genes, which can be grouped based on the RNA they produce and their functions. The main categories are: 1. rRNA Genes (Ribosomal RNA Genes) These genes produce ribos...
Read more

Describe the components of the promoter region of a eukaryotic gene

In eukaryotic genes, the promoter region is a special stretch of DNA that lies just before the gene. Its main job is to control when and where transcription starts. It does this by providing binding sites for RNA polymerase II and other transcription factors. The promoter region can be divided into two main parts: Core Promoter Proximal Promoter Elements Each of these parts has different types of DNA sequences that help start and regulate transcription. 1. Core Promoter This is the most essential part of the promoter and lies near the transcription start site  (called the +1 position).  It directly helps in assembling the transcription machinery. The core promoter usually includes the following elements: TATA Box: A short DNA sequence (TATAAA) usually located 25–35 base pairs upstream from +1 site. It helps in positioning  RNA polymerase II.  A special protein called TBP (TATA-binding protein) binds here to start the transcription complex. Initiator (Inr) Sequence: F...
Read more

What are the differences between gene enhancers and gene silencers? How do enhancers and silencers regulate eukaryotic gene expression?

Enhancers and silencers are two important types of regulatory DNA sequences that play opposite roles in controlling gene expression in eukaryotic cells. They are non-coding DNA elements which do not produce proteins but control when, where and how much a gene is expressed. They work by interacting with transcription factors and RNA polymerase to either increase or decrease the level of transcription. Differences Between Gene Enhancers and Gene Silencers Gene enhancers and gene silencers are both regulatory DNA elements found in eukaryotic genomes. Their main role is to control the level of gene expression, but they work in opposite directions. The differences between them can be explained based on the following criteria: 1. Based on Function Enhancers   increase  the transcription of a gene. They make the gene more active and allow it to produce more RNA. On the other hand,  silencers   reduce  or  completely block  transcription. They stop or decrease...
Read more

What is the difference between regulatory gene and structural gene?

Genes are basic units of heredity that carry instructions for the development and functioning of living organisms. Among various types of genes,  regulatory genes  and  structural genes  are essential for the proper functioning of cells, but their roles are quite different. Regulatory genes mainly control other genes, while structural genes directly code for proteins that form the body's structures or perform specific functions. To understand their differences clearly, we will compare them based on important criteria. 1. Based on Function The main function of  regulatory genes  is to control or regulate the expression of other genes. They produce regulatory proteins, such as repressors or activators, that influence whether structural genes are switched on or off. This control mechanism ensures that genes are expressed only when needed. In contrast,  structural genes  code directly for proteins or RNA molecules that are involved in building cellula...
Read more

Describe what happens when a nonsense mutation is introduced into the gene encoding transposase within a transposon

Transposons,  also known as  jumping genes,  are segments of DNA that can move from one position in the genome to another. This movement depends on a special enzyme called  transposase,  which is produced by a gene located inside the transposon itself. The transposase enzyme performs important functions like cutting the transposon from one place and helping it to insert into another. For the transposon to move, the transposase must be produced correctly and completely. When a  nonsense mutation  occurs in the transposase gene, it replaces a codon that normally codes for an amino acid with a  stop codon.  This causes the ribosome to stop protein synthesis early, resulting in a shortened and usually non-functional transposase enzyme. This leads to several important changes inside the cell. These changes are mainly: 1. Early Termination of Transposase Production The nonsense mutation introduces a premature stop codon in the transposase gene. Thi...
Read more

What are the regulatory sequences of a typical eukaryotic gene? Give examples

In eukaryotic cells, gene expression is highly controlled by specific regulatory DNA sequences. These sequences do not code for proteins, but they decide when, where and how much a gene should be expressed. They mainly control the process of  transcription,  where RNA is made from DNA. A typical eukaryotic gene contains several important regulatory sequences, such as: Promoters Enhancers Silencers Insulators Response elements 1. Promoter The promoter is the main regulatory region of a gene. It lies just before the  transcription start site,  which is the point where RNA starts getting made. This is the site where RNA polymerase and transcription factors attach to begin transcription. One well-known part of the promoter is the  TATA box,  found around 25 to 35 base pairs before the start site. It helps RNA polymerase find the correct place to begin. Another element, the  Initiator (Inr)  sequence, is present near the +1 position and supports proper...
Read more

Miller and Urey Experiment

Image
In the early 1950s, scientists were exploring how life might have originated on Earth from non-living matter. At that time, it was widely believed that the early Earth's atmosphere was reducing in nature, meaning it had very low oxygen and was rich in gases like methane (CH₄), ammonia (NH₃), hydrogen (H₂) and water vapor (H₂O). This idea was strongly supported by the Russian scientist A.I. Oparin and the British biologist J.B.S. Haldane in the 1920s and 1930s, who proposed that organic molecules essential for life could form spontaneously under such conditions. In 1952, Stanley L. Miller, a graduate student, conducted an experiment under the guidance of Harold C. Urey at the University of Chicago. The experiment aimed to test whether simple inorganic molecules could give rise to organic compounds under the conditions assumed to exist on primitive Earth. This experiment became famously known as the Miller-Urey Experiment  and its findings were published in 1953. Experimental Se...
Read more