Depurination

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Depurination

Diagram of an apurinic site resulting from depurination.

Depurination is a common form of DNA damage that involves the loss of a purine base (adenine or guanine) from the DNA molecule. This process results in the formation of an apurinic site, also known as an AP site, which can lead to mutations if not repaired.

Mechanism

Depurination occurs through the hydrolysis of the glycosidic bond between the purine base and the deoxyribose sugar in the DNA backbone. This reaction is spontaneous and can be accelerated by acidic conditions. The loss of a purine base leaves behind a deoxyribose sugar without its attached base, creating an apurinic site.

Consequences

The presence of an apurinic site in DNA can interfere with DNA replication and transcription. During replication, DNA polymerase may insert an incorrect base opposite the apurinic site, leading to a mutation. If left unrepaired, these mutations can accumulate and potentially lead to cancer or other genetic disorders.

Repair Mechanisms

Cells have evolved mechanisms to repair apurinic sites through the base excision repair (BER) pathway. In this process, an AP endonuclease recognizes the apurinic site and cleaves the DNA backbone at this location. This is followed by the removal of the deoxyribose sugar and the insertion of the correct nucleotide by DNA polymerase. Finally, DNA ligase seals the nick in the DNA backbone, completing the repair.

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Contributors: Prab R. Tumpati, MD