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Figure 4. Two types of mutations repaired by the nucleotide excision repair pathway. Ultraviolet light can trigger a chemical reaction that links adjacent thymines. Complex organic molecules such as benzo[a]pyrene can link on to a base such as guanine.

aflatoxin and benzo[^]pyrene are potent carcinogens. Ingestion or inhalation of these and similar compounds activates the body's detoxification systems, which convert the hydrophobic organic molecules into water-soluble forms for removal. However, the intermediate forms of aflatoxin and benzo[^]pyrene produced during the detoxification reaction happen to be very reactive with DNA purines, and form DNA base adducts (they "add on" to DNA). Specifically, such compounds tend to adduct guanine and, to a lesser extent, adenine. These large DNA adducts can cause mutations, and, since they block DNA replication, deletions of large segments of DNA can occur. Also, they activate the cell's damage surveillance systems, and, if not repaired, can cause cell death (apoptosis).

The mechanism of NER, involving some thirty proteins, is more complex than that of BER, but the basic principles are similar: damage recognition, damage excision, DNA repair synthesis, and DNA ligation (Figure 5). Damage recognition is obviously very important (Figure 5, step 1), but how can a single multiprotein complex detect so many different types of DNA damage? The answer is that the DNA damage must (1) distort the normal double-stranded structure of DNA, and/or (2) block transcription by RNA polymerase. Unusual kinks or twists in double-stranded DNA are recognized by the NER damage-recognition multiprotein complex. Also, when RNA polymerase stalls at a damaged DNA base, components of the NER damage-recognition complex are recruited to the site of damage.

carcinogens substances that cause cancer hydrophobic "water hating," such as oils

DNA crosslinks also interfere with another vital cellular process: transcription of genes by RNA polymerase.

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