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How does the DNA repair pathway known as base excision repair (BER) work on a molecular level and what are the key enzymes involved in this process?

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Base excision repair  BER  is a crucial DNA repair pathway that corrects small base lesions in the DNA, such as damaged bases, deaminated bases, and abasic sites, which can result from oxidation, alkylation, and deamination. This pathway is essential for maintaining genome stability and preventing mutations that can lead to various diseases, including cancer.On a molecular level, BER involves several key enzymes and proteins that work together in a coordinated manner to identify and repair the damaged DNA. The main steps of the BER pathway are as follows:1. Recognition and removal of the damaged base: The first step in BER is the recognition of the damaged base by a DNA glycosylase enzyme. There are several types of DNA glycosylases, each with specificity for different types of damaged bases. The glycosylase enzyme binds to the damaged base and cleaves the N-glycosidic bond between the base and the sugar phosphate backbone, leaving an abasic site  also known as an AP site .2. AP site cleavage: The abasic site is then recognized by an enzyme called AP endonuclease  APE1 in humans , which cleaves the phosphodiester bond 5' to the AP site, generating a single-strand break with a 3'-hydroxyl group and a 5'-deoxyribose phosphate  5'-dRP  group.3. Removal of the 5'-dRP group: The 5'-dRP group is removed by the action of a phosphodiesterase enzyme, such as DNA polymerase   Pol   in humans, which possesses both polymerase and 5'-dRP lyase activities.4. Gap filling: DNA polymerase  Pol  in humans  then adds the correct nucleotide to the 3'-hydroxyl group, using the undamaged complementary strand as a template.5. DNA ligation: Finally, the nick in the DNA strand is sealed by a DNA ligase enzyme  Ligase III in humans , which forms a phosphodiester bond between the 3'-hydroxyl group and the 5'-phosphate group, restoring the integrity of the DNA molecule.In summary, the base excision repair pathway is a highly coordinated process that involves several key enzymes, including DNA glycosylases, AP endonucleases, DNA polymerases, and DNA ligases, to identify and repair small base lesions in the DNA, maintaining genome stability and preventing the accumulation of mutations.

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