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How can DNA damage be repaired by base excision repair?

Base excision repair (BER) is a cellular mechanism that repairs DNA damage caused by the removal of damaged or incorrect bases from the DNA molecule. It is one of the major pathways involved in maintaining the integrity of the genome and preventing the accumulation of mutations.

1. Recognition and removal of damaged base

The first step in base excision repair is the recognition and removal of the damaged base. This is typically done by a DNA glycosylase enzyme, which recognizes specific types of damaged bases and cleaves the bond between the damaged base and the sugar-phosphate backbone of the DNA molecule. The glycosylase enzyme then leaves an apurinic/apyrimidinic (AP) site, also known as an abasic site, in the DNA.

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2. Incision of the DNA backbone

After the damaged base is removed, an AP endonuclease enzyme recognizes the AP site and cleaves the DNA backbone on one side of the site. This creates a single-stranded DNA gap with a free 3′ hydroxyl group and a 5′ phosphate group.

3. DNA synthesis and ligation

Next, a DNA polymerase enzyme fills in the single-stranded DNA gap with the correct nucleotides, using the undamaged DNA strand as a template. The DNA polymerase also removes the 5′ phosphate group and replaces it with a 5′ hydroxyl group. Finally, a DNA ligase enzyme seals the nick in the DNA backbone, completing the repair process.

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Base excision repair is an important mechanism for repairing DNA damage caused by various factors, including oxidative stress, exposure to certain chemicals, and spontaneous hydrolysis. By efficiently repairing damaged bases, BER helps to maintain the stability and integrity of the genome, reducing the risk of mutations and promoting cellular longevity.

Keywords: damaged, repair, enzyme, excision, backbone, damage, removal, phosphate, cellular