DNA Repair // Chapter 6 // BIO115

Chemical modifications of nucleotides, if left unpaired, produce mutations.

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Cells can repair double-strand breaks in one of two ways.

1. homologous end joining 2.homolohous recombination (continued-type later)

Depurination and deamination are the most frequent chemical reactions known to create serious DNA damage in cells.

Deprivation can remove guanine (or adenine) from DNA. The major type of deamination reaction converts cytosine to an altered DNA bar, uracil; however, deamination can also occur on other bases as well. Both depurination and deamination take place on double-helical DNA, and neither break the phosphodiester backbone.

Errors made during DNA replication must be corrected to avoid mutations.

If uncorrected, a mismatch will lead to a permanent mutation in one of the two DNA molecules produced by the next round of DNA replication.

The basic mechanism of DNA repair involves three steps.

In step 1 (excision), the damage is cut out by one of a series of nucleases, each specialized for a type of DNA damage. In step 2 (resynthesis), the original DNA sequence is restored by a repair DNA polymerase, which fills in the gap created by the excision events. In step 3 (ligation), DNA ligase seals the nick left in the sugar-phosphate backbone of the repaired strand. Nick sealing, which requires energy from ATP hydrolysis, remakes the adjacent nucleotides.

Homologous recombination allows the flawless repair of DNA double-strand breaks.

This is the preferred method for repairing double-strand breaks that arise shortly after the DNA has been replicated but before the cell has divided.

The ultraviolet radiation in sunlight can cause the formation of thymine dimers.

Two adjacent thymine bases have become covertly attached to each other to form a thymine dimer. Skin cells that are exposed to sunlight are especially susceptible to this type of DNA damage.

Mismatch repair eliminates replication error and restores the original DNA sequence.

When mistakes occur during DNA replication, the repair machinery must replace the incorrect nucleotide on the newly synthesized strand, using the original parent strand as its template. This mechanism eliminates the mutation.

A single nucleotide change causes the disease sickle-cell anemia

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Cancer incidence increases dramatically with age.

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The sex-determination genes from humans and whales are unmistakably similar.

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