Mutagens

Chemical and physical mutagens can cause mutations by replacing one base with another in the DNA molecule, causing structural changes in a base so that it causes it to mispair, causing insertions or deletions, or damaging a base so much that it is unable to pair with any other normal base. Base analogs are sufficiently similar to the normal nitrogenous bases in DNA that they can be incorporated into a replicating DNA molecule by DNA polymerases. Once incorporated, however, base analogs have abnormal base-pairing properties so that they produce mutations during subsequent DNA replication cycles. For example, 5-bromouracil and 2- amino-purine are two common base analogs.

Alkylating agents cause mutations by chemically altering bases so that they pair up with a specific base other than the normally complementary base. Intercalating agents are planar molecules that can insert themselves between the stacked bases within the double helix. These agents alter the molecule of DNA in such a way that DNA polymerases may insert or skip one or more bases during replication, often resulting in frameshift mutations. For example, proflavin, acridine orange, and ethidium bromide are intercalators.

When ultraviolet light is absorbed by adjacent pyrimidines in one strand of a DNA molecule, a dimer forms. These dimers interfere with proper base pairing during DNA replication. The impact is so extensive that the normal replicative process is stopped until these dimers are repaired.

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