Nucleotide Excision Repair And Crosslink Repair

Processes like the hydrolytic deamination of cytosine or the oxidation of guanine lead to altered bases with an increased potential for mispairing. However, neither change interferes principally with DNA replication or transcription. This is different for some other types of damage inflicted on DNA. Ultraviolet radiation (UV) causes chemical reactions in DNA. UV radiation with wavelengths in the absorption maximum of DNA cannot penetrate into the body (—>12.1), but the UVB range from 280-320 nm can and just reaches into the absorption spectrum of DNA. This type of UV induces mainly reactions between adjacent pyrimidine bases such as thymine-thymine cyclobutane dimers and thymine-cytosine (or cytosine-cytosine) 6-4 photoproducts (Figure 3.5). These intra-strand dimers present obstacles to transcription and replication of DNA.

Thym me-thymine Thymine-cytosine cyclobutane dimer 6—>4 product

Figure 3.5 Pyrimidine base reactions induced by UV irradiation

Likewise, chemical reactions of endogenous compounds and activated chemical carcinogens can lead to modified bases that are too bulky to fit into a double helix and cannot be recognized by polymerases. Adducts of aflatoxin or benzopyrene at guanines are important examples (Figure 3.6). Even proteins can become covalently linked to DNA bases. Transcription and replication are also prevented, when opposite DNA strands in the double helix are crosslinked. This is exploited in cancer therapy by compounds like cis-platinum and mitomycin C (^22.2).

Aflatoxin Benzopyrene

Reactive oxygen species y

Alkylating agents

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