Base Analogs and Mutagens

This page discusses some general mechanisms of mutation by base analogs and chemical mutagens.

Base Analogs

A base analog is a chemical that shares structural similarity with one of the 4 DNA bases (G, A, T and C). Common examples are 5-bromouracil (5-Bu) and 2-aminopurine (2-AP). Due to the structural similarity to bases, if these chemicals are present then they will be incorporated into nucleotides. These nucleotides will then be utilized like another nucleotide by the cellular machinery during polymerization reactions. As a result, the base analogs will end up in the cell's DNA.

In the section on repair, enzymes are discussed that can potentially recognize these base analogs once they have been incorporated into DNA and repair the DNA by removing them. Many base analogs, however, are more prone to alternate base-pairing than the 4 "normal" bases. If base analogs are not repaired prior to replication they will be read as a template by the replication apparatus, and because they are more prone to alternate pairings there is an increased chance that the incorrect nucleotide will be incorporated by polymerase. Once this has happened the cell will use the "real" DNA base (in the "real base"-base analog base pair) in any repair. This results in a mutation since the real base is not the real base that was present at that position prior to the base analog being incorporated.

For example, 5-BU base-pairs stably with both A and G (although more stably with A). If 5Bu is present and one gets incorporated opposite an A then there will be an A:5Bu base pair. If this is not repaired before the next replication round, then there is an increased frequency (relative to if it were an A:T base pair) that the polymerase would incorporate a G so that the new DNA molecule has a G:5Bu base pair. Once this exists in the DNA, any repair by the cell would remove the 5Bu - as an "incorrect base" - and replace it with a C so that there is a G:C base pair. The end result is a transition from A to G.

Chemical Mutagens

This class of mutagens alter the structure of DNA which results in mutation as will be discussed. Since the chemicals react with DNA their effects can occur at any time - unlike the influence of base analogs that are only mutagenic during the replication process. Some mutagens are:

• Alkylating agents: Alkylating agents, such as ethyl methane sulfonate (EMS), transfer an alkyl group to bases. They have a wide range of mutagenic effects that arise from this alteration.


• Intercalating agents: The most commonly encountered of these is ethidium bromide which is frequently used in laboratories to stain DNA. These are hydrophobic molecules that fit between the stacked base-pairs of a dsDNA molecule. In an aqueous solution these molecules will intercalate and force some degree of unwinding of the helix.


• Deaminating agents: Deaminating agents, such as nitrous acid convert the amino group of a base to a keto group. This can alter any A, G or C (Thymine does not have an amino group to remove). The alteration changes the base-pairing properties which - if the base is not repaired - will lead to misincorporation in the next round of replication. For example, deaminaton of A leads to the formation of the base hypoxanthine which pairs with cytosine. Therefore, deamination changes an A:T pair to an H:T pair. If this is not repaired, the next replication that uses H as a template will result in an H:C pair. Eventually, this will be repaired or replicated to a G:C pair - a mutation from the original A:T.


• Hydroxylating agents: Hydroxylamine reacts with cytosine resulting in a hydroxylated amino group on this base. Hydroxylated cytosines base-pair with A so an unprepared G:hC base pair will result in an A:hC base pair after replication, and eventually an A:T base pair after repair or another round of replication.