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Breast and ovarian cancer

Breast and ovarian cancer

sources: Modified from A. Kornberg and T. Baker, 1992, DNA Replication, 2d ed., W. H. Freeman and Company, p. 788; J. Hoeijmakers, 2001, Nature 411:366; and L. Thompson and D. Schild, 2002, Mutation Res. 509:49.

Base Excision Is Used to Repair Damaged Bases and Single-Base Mispairs

In humans, the most common type of point mutation is a C to T, which is caused by deamination of 5-methyl C to T (see Figure 23-25). The conceptual problem with base excision repair is determining which is the normal and which is the mutant DNA strand, and repairing the latter so that it is properly base-paired with the normal strand. But since a G • T mismatch is almost invariably caused by chemical conversion of C to U or 5-methyl C to T, the repair system "knows" to remove the T and replace it with a C. The G • T mismatch is recognized by a DNA glycosylase that flips the thymine base out of the helix and then hydrolyzes the bond that connects it to the sugar-phosphate DNA backbone. Following this initial incision, the segment of the damaged strand containing the baseless deoxyribose is excised by an AP endonuclease that cuts the DNA strand near the abasic site. The resultant single-stranded gap in the damaged strand is filled in by a DNA polymerase and sealed by DNA ligase, restoring the original G • C base pair.

DNA glycosylase

Il II

APEI endonuclease

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