DNA can undergo spontaneous changes in its chemistry that result in both
deletions and substitutions. DNA naturally loses purine bases at times in a
process called apurination. Most often, a purine’s lost when the bond
between adenine and the sugar, deoxyribose, is broken. (See Chapter 6 for a
reminder of what a nucleotide looks like.) When a purine is lost, replication
treats the spot occupied by the orphaned sugar as if it never contained a
base at all, resulting in a deletion.
Tuesday, April 14, 2009
Deamination
Deamination is another chemical change that occurs naturally in DNA. It’s
what happens when an amino group (composed of a nitrogen atom and two
hydrogens, NH2) is lost from a base. Figure 13-4 shows the before and after
stages of deamination. When cytosine loses its amino group, it’s converted to
uracil. Uracil normally isn’t found in DNA at all because it’s a component of
RNA. If uracil appears in a DNA strand, replication replaces the uracil with a
thymine, creating a substitution error. Until it’s snipped out and replaced
during repair (see “Evaluating Options for DNA Repair” later in this chapter),
uracil acts as a template during replication and pairs with adenine.
Ultimately, what was a C-G pair transitions into an A-T pair instead.
what happens when an amino group (composed of a nitrogen atom and two
hydrogens, NH2) is lost from a base. Figure 13-4 shows the before and after
stages of deamination. When cytosine loses its amino group, it’s converted to
uracil. Uracil normally isn’t found in DNA at all because it’s a component of
RNA. If uracil appears in a DNA strand, replication replaces the uracil with a
thymine, creating a substitution error. Until it’s snipped out and replaced
during repair (see “Evaluating Options for DNA Repair” later in this chapter),
uracil acts as a template during replication and pairs with adenine.
Ultimately, what was a C-G pair transitions into an A-T pair instead.
Induced mutations
Induced mutations result from exposure to some outside agent such as chemicals
or radiation. It probably comes as no surprise to you to find out that
many chemicals can cause DNA to mutate. Carcinogens (chemicals that cause
cancers) aren’t uncommon; the chemicals in cigarette smoke are probably
the biggest offenders. In addition to chemicals that cause mutations, sources
of radiation, from X-rays to sunlight, are also mutagenic. A mutagen is any
factor that causes an increase in mutation rate. Mutagens may or may not
have phenotypic effects — it depends on what part of the DNA is affected.
The following sections cover two major categories of mutagens: chemicals
and radiation. Each causes different damage to DNA.
or radiation. It probably comes as no surprise to you to find out that
many chemicals can cause DNA to mutate. Carcinogens (chemicals that cause
cancers) aren’t uncommon; the chemicals in cigarette smoke are probably
the biggest offenders. In addition to chemicals that cause mutations, sources
of radiation, from X-rays to sunlight, are also mutagenic. A mutagen is any
factor that causes an increase in mutation rate. Mutagens may or may not
have phenotypic effects — it depends on what part of the DNA is affected.
The following sections cover two major categories of mutagens: chemicals
and radiation. Each causes different damage to DNA.
Chemical mutagens
The ability of chemicals to cause permanent changes in the DNA of organisms
was discovered by Charlotte Auerbach in the 1940s (see the sidebar “The
chemistry of mutation” for the full story). There are many types of mutagenic
chemicals; the following sections address four of the most common.
was discovered by Charlotte Auerbach in the 1940s (see the sidebar “The
chemistry of mutation” for the full story). There are many types of mutagenic
chemicals; the following sections address four of the most common.
Base analogs
Base analogs are chemicals that are structurally very similar to the bases
normally found in DNA. Base analogs can get incorporated into DNA during
replication because of their structural similarity to normal bases. One base
analog, 5-Bromouracil, is almost identical to the base thymine. Most often,
5-bromouracil (also known as 5BU), which is pictured in Figure 13-5, gets
incorporated as a substitute for thymine and as such is paired with adenine.
The problem arises when DNA replicates again with 5-bromouracil as part of
the template strand; 5BU’s mistaken for a cytosine and gets mispaired with
guanine. The series of events looks like this: 5-bromouracil is incorporated
where thymine used to be, so T-A becomes 5BU-A. After one round of replication,
the pair is 5BU-G because 5BU is prone to chemical changes that make
it a mimic of cytosine, the base normally paired with guanine. After a second
of replication, the pair ends up as C-G because 5BU isn’t found in normal DNA.
Thus, an A-T ends up as a C-G pair.
normally found in DNA. Base analogs can get incorporated into DNA during
replication because of their structural similarity to normal bases. One base
analog, 5-Bromouracil, is almost identical to the base thymine. Most often,
5-bromouracil (also known as 5BU), which is pictured in Figure 13-5, gets
incorporated as a substitute for thymine and as such is paired with adenine.
The problem arises when DNA replicates again with 5-bromouracil as part of
the template strand; 5BU’s mistaken for a cytosine and gets mispaired with
guanine. The series of events looks like this: 5-bromouracil is incorporated
where thymine used to be, so T-A becomes 5BU-A. After one round of replication,
the pair is 5BU-G because 5BU is prone to chemical changes that make
it a mimic of cytosine, the base normally paired with guanine. After a second
of replication, the pair ends up as C-G because 5BU isn’t found in normal DNA.
Thus, an A-T ends up as a C-G pair.
Alkylating agents
Like base analogs, alkylating agents induce mispairings between bases.
Alkylating agents, such as the chemical weapon mustard gas, add chemical
groups to the existing bases that make up DNA. As a consequence, the
altered bases pair with the wrong complement, thus introducing the mutation.
Surprisingly, alkylating agents are often used to fight cancer as part
of chemotherapy; therapeutic versions of alkylating agents may inhibit
cancer growth by interfering with the replication of DNA in rapidly dividing
cancer cells.
Alkylating agents, such as the chemical weapon mustard gas, add chemical
groups to the existing bases that make up DNA. As a consequence, the
altered bases pair with the wrong complement, thus introducing the mutation.
Surprisingly, alkylating agents are often used to fight cancer as part
of chemotherapy; therapeutic versions of alkylating agents may inhibit
cancer growth by interfering with the replication of DNA in rapidly dividing
cancer cells.
Unusually reactive forms of oxygen
Some forms of oxygen, called free radicals, are unusually reactive, meaning
they react readily with other chemicals. These oxygens can damage DNA
directly (by causing strand breaks) or can convert bases into new unwanted
chemicals that, like most other chemical mutagens, then cause mispairing
during replication. Free radicals of oxygen occur normally in your body as a
product of metabolism, but most of the time, they don’t cause any problems.
Certain activities, such as cigarette smoking and high exposure to radiation,
pollution, and weed killers, increase the number of free radicals in your
system to dangerous levels.
they react readily with other chemicals. These oxygens can damage DNA
directly (by causing strand breaks) or can convert bases into new unwanted
chemicals that, like most other chemical mutagens, then cause mispairing
during replication. Free radicals of oxygen occur normally in your body as a
product of metabolism, but most of the time, they don’t cause any problems.
Certain activities, such as cigarette smoking and high exposure to radiation,
pollution, and weed killers, increase the number of free radicals in your
system to dangerous levels.
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