14.4 (Mechanisms that correct replication errors) Vocab and Concepts

Mispaired bases are too large or small to maintain the correct separation of the strands of the double helix, and they cannot form the hydrogen bonds characteristic of the normal base pairs.

As a result, base mismatches distort the structure of the DNA helix. These distortions provide recognition sites for the enzymes catalyzing mismatch repair

the repair enzymes detect the mispaired base, cut the new DNA strand on each side of the mismatch, and remove a portion of the chain.

DNA polymerase fills in the gap with new DNA. the repair is completed by DNA ligase, which seals the nucleotide chain into a continuous DNA molecule

base-pair mismatches

DNA polymerases make very few errors as they assemble new nucleotide chains. Most of the mistakes that do occur are corrected, either by a proofreading mechanism carried out during replication by the DNA polymerases themselves or by a DNA repair mechanism that corrects mismatched base pairs after replication is complete

Similar repair systems

also detect and correct alterations in DNA caused by the damaging effects of chemicals and radiation, including the ultraviolet light in sunlight. Ex: skin cancer is likely with xeroderma pigmentosum, a hereditary disorder in which the repair mechanism is faulty

proofreading mechanism

first proposed in 1972 by Kornberg/Brutlag, depends on the ability of DNA polymerases to back up and remove mispaired nucleotides from a DNA strand. For most of the polymerization reactions, DNA polymerase adds the correct nucleotide to the growing chain. But the polymerase also has a small window of time for proofreading. If a newly added nucleotide is mismatched, the DNA polymerase reverses, using a built-in 3 →5 exonuclease activity to remove the newly added incorrect nucleotide. the enzyme then resumes forward synthesis, now inserting the correct nucleotide

DNA mismatch repair mechanisms

increase the accuracy of DNA replication well beyond the one-in-a million errors that persist after proofreading. the mechanisms operate similarly in all organisms

when the E. coli DNA polymerase III is fully functional,

its overall error rate is astonishingly low with only about 1 mispair surviving in the DNA for every 1 million nucleotides polymerized in the test tube. If the proofreading activity of the enzyme is experimentally inhibited, the error rate increases to about 1 mistake for every 1,000 to 10,000 nucleotides polymerized. Experiments with eukaryotes have yielded similar results.

mutations

the errors that persist, although extremely rare. differences in DNA sequence that appear and remain in the replicated copies. When a mutation occurs in a gene, it can alter the property of the protein encoded by the gene, which, in turn, may alter how the organism functions. Hence, mutations are highly important to the evolutionary process because they are the ultimate source of the variability in offspring acted on by natural selection