Other Types of DNA Repair

The DNA repair pathways described so far respond to damage that is limited to one strand of a DNA molecule, leaving the other strand to be used as a template for the synthesis of new DNA during the repair process. Some types of DNA damage, however, affect both strands of the molecule and therefore pose a more severe challenge to the DNA repair machinery. Ionizing radiation frequently results in doublestrand breaks in DNA. The repair of double-strand breaks is frequently by homologous recombination. Models for homologous recombination were described in Chapter 12.

Another type of damage that affects both strands is an interstrand cross-link, which arises when the two strands of a duplex are connected through covalent bonds. Interstrand cross-links are extremely toxic to cells because they halt replication. Several drugs commonly used in chemotherapy, including cisplatin, mitomycin C, psoralen, and nitrogen mustard, cause interstrand cross-links. Nitrogen mustard, which is structurally related to the mustard gas used by Charlotte Auerbach to induce mutations in Drosophila, was the first chemical agent to be used in chemotherapy treat

ffi Damage to the DNA, distorts the configuration of the molecule.

Damaged DNA

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