Key Concepts of Section 5.6

• Changes in the DNA sequence result from copying errors and the effects of various physical and chemical agents.

• Many copying errors that occur during DNA replication are corrected by the proofreading function of DNA polymerases, which can recognize incorrect (mispaired) bases at the 3′ end of the growing strand and then remove them by means of an inherent 3′→5′ exonuclease activity (see Figure 5-33).

• Eukaryotic cells have three excision-repair systems for correcting mispaired bases and for removing chemical adducts from DNA. Base excision repair, mismatch repair, and nucleotide excision repair operate with high accuracy and generally do not introduce errors.

• Repair of double-strand breaks by the nonhomologous end joining pathway can link segments of DNA from different chromosomes, possibly forming an oncogenic chromosomal translocation. This repair mechanism also produces a small deletion, even when segments from the same chromosome are joined.

• Error-free repair of double-strand breaks in DNA is accomplished by homologous recombination using the undamaged sister chromatid as a template.

• Inherited defects in the nucleotide excision-repair pathway, as in individuals with xeroderma pigmentosum, predispose them to skin cancer. Inherited colon cancer is frequently associated with mutant forms of proteins essential for the mismatch repair pathway. Defects in repair by homologous recombination are associated with inheritance of one mutant allele of the BRCA-1 or BRCA-2 gene and result in predisposition to breast and uterine cancer.