Base excision repair

Base excision repair (BER) is a cellular process that corrects DNA damage caused by oxidation, deamination, or alkylation. These types of damage can lead to changes in the structure of the DNA molecule, potentially leading to mutations and genetic diseases.

Mechanism

The process of base excision repair involves several steps. First, a DNA glycosylase enzyme recognizes and removes the damaged base, leaving behind an apurinic/apyrimidinic site (AP site). This is followed by the action of an AP endonuclease, which cleaves the phosphodiester bond in the DNA backbone at the AP site. The resulting gap is then filled in by a DNA polymerase, which adds the correct nucleotide, and a DNA ligase, which seals the nick in the DNA backbone.

There are two sub-pathways of BER: short-patch BER, which replaces a single nucleotide, and long-patch BER, which replaces 2-10 nucleotides.

DNA glycosylases

DNA glycosylases are a family of enzymes involved in base excision repair. They are responsible for identifying and removing the damaged base, initiating the repair process. There are several different types of DNA glycosylases, each of which recognizes and removes a specific type of damaged base.

AP endonucleases

AP endonucleases are enzymes that recognize and cleave the DNA backbone at the AP site left by the action of a DNA glycosylase. This creates a gap in the DNA molecule that can be filled in by a DNA polymerase.

DNA polymerases

DNA polymerases are enzymes that synthesize new DNA molecules by copying a DNA template strand. In the context of base excision repair, a DNA polymerase fills in the gap left by the action of an AP endonuclease, adding the correct nucleotide to replace the damaged base.

DNA ligases

DNA ligases are enzymes that join two DNA strands together by forming a phosphodiester bond. In the context of base excision repair, a DNA ligase seals the nick in the DNA backbone after the correct nucleotide has been added by a DNA polymerase.

Clinical significance

Defects in base excision repair can lead to an increased risk of cancer, as DNA damage that is not properly repaired can lead to mutations. In addition, certain neurological disorders and aging-related diseases have been linked to defects in base excision repair.

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  BER basic pathway

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  8-oxoG forming Hoogsteen base pair with dA

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  Uracil base glycosidase

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  Desaminierung C to U

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  Demethylation of 5-methylcytosine