oxidized pyrimidine nucleobase lesion DNA N-glycosylase activity

Definition

Target type: molecularfunction

Catalysis of the removal oxidized pyrimidine bases by cleaving the N-C1' glycosidic bond between the oxidized pyrimidine and the deoxyribose sugar. The reaction involves formation of a covalent enzyme-pyrimidine base intermediate. Release of the enzyme and free base by a beta-elimination or a beta, gamma-elimination mechanism results in the cleavage of the DNA backbone 3' of the apyrimidinic (AP) site. [GOC:elh, PMID:11554296]

Oxidized pyrimidine nucleobase lesion DNA N-glycosylase activity is a crucial DNA repair mechanism that specifically removes damaged pyrimidine bases from DNA. These damaged bases, which can be formed through exposure to reactive oxygen species, can disrupt DNA replication and transcription, leading to mutations and cellular dysfunction.

The enzyme responsible for this activity, known as a DNA glycosylase, recognizes and cleaves the glycosidic bond between the damaged pyrimidine base and the deoxyribose sugar backbone. This leaves a gap in the DNA strand, known as an abasic site. The abasic site is then processed by other DNA repair enzymes, including an AP endonuclease that cleaves the phosphodiester backbone, followed by a DNA polymerase that fills the gap with the correct nucleotide, and a DNA ligase that seals the nick.

This process ensures the integrity of the genetic code and prevents the accumulation of mutations that can lead to cancer and other diseases. The specific substrates for oxidized pyrimidine nucleobase lesion DNA N-glycosylase activity include thymine glycol, 5-hydroxycytosine, 5-formylcytosine, and 5-carboxylcytosine. These oxidized pyrimidines are all formed by the reaction of reactive oxygen species with the DNA base, causing structural damage and hindering DNA replication and transcription.

The N-glycosylase activity is highly specific for these damaged bases, ensuring that the correct base is removed and replaced, preventing the accumulation of mutations.

In addition to its role in DNA repair, oxidized pyrimidine nucleobase lesion DNA N-glycosylase activity is also involved in other cellular processes, such as DNA replication and transcription. It plays a critical role in maintaining the stability and integrity of the genome, and its dysfunction can lead to various diseases, including cancer, neurodegenerative disorders, and premature aging.'
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Proteins (3)

Compounds (1)