8 DNA Excision Repair Pathways

Abstract

Most life forms have the ability to respond to alterations in genomic DNA that occur spontaneously or are caused by environmental agents. Generally, these responses take one of two forms. Cells can either repair the damage and restore the genome to its normal physical and functional state, or they can tolerate lesions in a way that reduces their lethal effects (Friedberg et al. 1995). This brief overview exclusively considers the former cellular response to DNA damage, which represents true DNA repair. However, the tolerance of base damage, typically by replicative bypass, sets the stage for permanent mutations in DNA. In fact, a major function of DNA repair is the prevention of mutations, which can have significant phenotypic consequences, including neoplastic transformation in mammalian cells (Friedberg et al. 1995). The repair of altered bases in DNA is frequently classified into two major categories that have important mechanistic distinctions. A relatively limited group of lesions in DNA can be repaired in single-step reactions that directly reverse the damage. The light-dependent monomerization of cyclobutane pyrimidine dimers by DNA photolyase is a well-characterized example (Kim and Sancar 1993). DNA photolyases have been extensively characterized from many prokaryotes and fungi, and from vertebrates, including fish (Yasuhira and Yasui 1992) and marsupials (Yasui et al. 1994). However, this mode for the repair of the quantitatively major form of DNA damage induced by ultraviolet (UV) radiation seems to have been lost in placental mammals (Li et al. 1993). The direct removal of small alkyl groups (such as...