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7.2: Riparazione per escissione di basi
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Molecular Biology

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Base Excision Repair
 
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7.2: Base Excision Repair

One of the common DNA damages is the chemical alteration of single bases by alkylation, oxidation, or deamination. The altered bases cause mispairing and strand breakage during replication. This type of damage causes minimal change to the DNA double helix structure and can be repaired by the base excision repair (BER) pathways. BER corrects damaged DNA sequences by removing the damaged base and restoring the original base sequence using the complementary strand as a template.

The first step of BER is the recognition of DNA damage, which is done by DNA glycosylases. Depending on the type of base, a specific glycosylase cuts the N-glycosidic bond between the nucleotide base and ribose, leaving the phosphate backbone of the DNA intact but creating an apurinic or apyrimidinic (AP) site. Bifunctional glycosylases make an incision in the phosphodiester chain, resulting in the formation of a 5’ or 3’ phosphate. Monofunctional glycosylases do not exhibit this property and have to depend on an AP Endonuclease to cleave the sugar-phosphate link, 5’ to the abasic site, producing a 3’OH and a 5’ deoxyribophosphate. Based on the corresponding W-C pairing, DNA polymerase inserts the correct base and uses its associated AP-lyase activity to remove the deoxyribose phosphate. The nick in the backbone is sealed by DNA ligase. Both DNA ligase III and DNA polymerase use the protein XRCC1 as a scaffold to bind the site of repair.

Mutations in the proteins of the BER pathways can lead to various types of cancer. For example, a mutation in the human glycosylase OGG1 is associated with an increased risk for lung and pancreatic cancers.


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