BSCI 10001 Lecture Notes - Lecture 19: Hereditary Nonpolyposis Colorectal Cancer, Xeroderma Pigmentosum, Aziz Sancar

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(1) accurate selection of nucleotides to start with; (2) immediate proofreading; Dna polymerases are remarkably accurate; the wrong nucleotide is incorporated only. But the overall error rate is actually much less than 10- 5, because pol iii detects an incorrect nucleotide after it has incorporated it into the growing chain. It stops, backs up, excises the mismatched base, incorporates the correct base, and then continues on. The proofreading activity of pol iii detects and repairs an incorrectly added base about 99 times out of a hundred. Proofreading therefore decreases the error rate of pol iii from 10-5 to 10-7. But the actual observed overall error frequency of dna replication is even lower another one hundred fold lower: 10-9 ! This is because repair enzymes run along behind the polymerase, scanning the completed double helix for mismatch errors; eg, a g-t pair.

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