Depyrimidination

Depyrimidination is a type of DNA damage that occurs when a pyrimidine base, cytosine or thymine, is spontaneously lost from the DNA strand. This process is an endogenous DNA damage event, meaning it arises from within the cell rather than from external agents like radiation or chemicals. The purine bases, adenine and guanine, are much less susceptible to depurination. Depyrimidination results in an abasic site, also known as an apurinic or apyrimidinic (AP) site, where a nucleotide is missing its base.

These abasic sites are highly mutagenic if not repaired. They can lead to mispairing during DNA replication, where the DNA polymerase inserts an incorrect nucleotide opposite the abasic site. This can result in point mutations, such as transversions or transitions, within the DNA sequence. The accumulation of such mutations can have significant consequences for cellular function and organismal health, potentially contributing to diseases like cancer.

Cells possess sophisticated DNA repair mechanisms to counteract depyrimidination. The primary pathway for repairing abasic sites is the base excision repair (BER) pathway. In BER, specific enzymes called AP endonucleases recognize and cleave the DNA backbone at the abasic site. This allows for the removal of the sugar-phosphate backbone and the subsequent insertion of a new nucleotide with the correct base by DNA polymerase, followed by ligation to seal the strand. Efficient and accurate functioning of the BER pathway is crucial for maintaining genomic integrity.