Connecting Concepts

The Basic Pathway of DNA Repair

We have now examined several different mechanisms of DNA repair. What do these methods have in common? How are they different? Most methods of DNA repair depend on the presence of two strands, because nucleotides in the damaged area are removed and replaced. Nucleotides are replaced in mismatch repair, base excision repair, and nucleotide-excision repair, but are not replaced by direct-repair mechanisms.

Repair mechanisms that include nucleotide removal utilize a common four-step pathway:

1. Detection: The damaged section of the DNA is recognized.

2. Excision: DNA repair endonucleases nick the phosphodiester backbone on one or both sides of the DNA damage.

3. Polymerization: DNA polymerase adds nucleotides to the newly exposed 3'-OH group by using the other strand as a template and replacing damaged (and frequently some undamaged) nucleotides.

4. Ligation: DNA ligase seals the nicks in the sugar -phosphate backbone.

The primary differences in the mechanisms of mismatch, base-excision, and nucleotide-excision repair are in the details of detection and excision. In base-excision and mismatch repair, a single nick is made in the sugar -phosphate backbone on one side of the damaged strand; in nucleotide-excision repair, nicks are made on both sides of the DNA lesion. In base-excision repair, DNA polymerase displaces the old nucleotides as it adds new nucleotides to the 3' end of the nick; in mismatch repair, the old nucleotides are degraded; and, in nucleotide-excision repair, nucleotides are displaced by helicase enzymes. All three mechanisms use DNA polymerase and ligase to fill in the gap produced by the excision and removal of damaged nucleotides.

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DNA repair

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