For example, DNA photolyases can directly reverse the two major forms of UV-induced lesions. The most straightforward method of repairing DNA damage is the direct reversal of the lesion. 8 The majority of these repair pathways preserve the genetic information without introducing errors either by directly reversing the damage or by using an undamaged template strand to accomplish error-free repair ( Figure 2). Cells have repair systems to remove these harmful lesions and thus preserve the integrity of their genomes. Modified or otherwise damaged DNA bases can be mutagenic and are potentially cytotoxic. 1, 2 It is this cytotoxic effect that forms the mechanistic basis of action of many of the anticancer drugs currently in use today. It has been estimated that as few as 20 interstrand cross-links in the bacterial or mammalian genome can be lethal to cells that lack the ability to remove the cross-link. If left intact, interstrand cross-links can lead to cell death. Interstrand cross-links prevent DNA strand separation and can thus act as absolute blocks to DNA replication and/or DNA transcription. Certain agents, however, including bifunctional alkylating agents, platinum compounds, and psoralen can produce covalent adducts with DNA bases on both strands of DNA, leading ultimately to the formation of interstrand cross-links ( Figure 1). Many of these lesions, in the form of base or phosphate modifications, occur on one or the other strand of DNA. The lesions produced by these chemical reactions can lead to mutations and/or cell death.
Cellular DNA is susceptible to chemical modifications when exposed to various environmental agents, chemotherapeutic agents, or endogenous agents produced by cellular processes.
0 kommentar(er)
