depurination

Definition

Target type: biologicalprocess

The disruption of the bond between the sugar in the backbone and the A or G base, causing the base to be removed and leaving a depurinated sugar. [GOC:ai]

Depurination is a spontaneous chemical reaction that occurs in DNA, involving the loss of a purine base (adenine or guanine) from the DNA backbone. This process is initiated by the hydrolysis of the glycosidic bond that connects the purine base to the deoxyribose sugar, leaving an apurinic site (AP site). The AP site is highly unstable and susceptible to further degradation.

Depurination occurs at a rate of approximately 10,000 events per day per mammalian cell. This relatively high frequency of depurination is due to the inherent instability of the glycosidic bond, particularly in the presence of elevated temperatures or reactive oxygen species.

The mechanism of depurination involves the following steps:

1. **Protonation of the N7 position of the purine base:** The nitrogen atom at position 7 of the purine base is protonated by a water molecule.

2. **Cleavage of the glycosidic bond:** The protonation of the N7 position weakens the glycosidic bond, facilitating its hydrolysis. The purine base is released from the DNA backbone, leaving an AP site.

3. **Formation of an AP site:** The AP site consists of a deoxyribose sugar that lacks a base.

Depurination has significant consequences for DNA integrity. The absence of a purine base at an AP site disrupts the Watson-Crick base pairing and can lead to errors during DNA replication. The AP site can also block DNA polymerase, halting replication. If not repaired, these errors can lead to mutations and genomic instability.

The cell has evolved sophisticated DNA repair mechanisms to counteract the deleterious effects of depurination. These mechanisms include:

1. **Base excision repair (BER):** The most common pathway for repairing AP sites. BER involves the sequential removal of the AP site by a DNA glycosylase, followed by cleavage of the phosphodiester bond by an AP endonuclease. The gap is then filled by DNA polymerase and ligated by DNA ligase.

2. **Nucleotide excision repair (NER):** This pathway is less efficient than BER but can repair a wider range of DNA lesions, including bulky adducts and thymine dimers.

3. **Translesion synthesis (TLS):** A bypass mechanism that allows DNA replication to proceed through a damaged DNA region. TLS utilizes specialized DNA polymerases that can tolerate lesions and insert a nucleotide opposite the AP site, although with a high error rate.

Depurination is a continuous and unavoidable process in living organisms. However, the efficient DNA repair mechanisms ensure that most of these lesions are repaired before they lead to mutations and disease. Dysregulation of DNA repair pathways, particularly BER, has been implicated in various human diseases, including cancer.

In summary, depurination is a fundamental process in DNA damage that involves the loss of a purine base from the DNA backbone. It disrupts DNA integrity and can lead to mutations and genomic instability. The cell has evolved sophisticated DNA repair mechanisms to minimize the consequences of depurination. Understanding the biological process of depurination is crucial for understanding DNA repair mechanisms and the pathogenesis of various human diseases.'"

Proteins (4)

Compounds (9)