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Knex 78780 - Education DNA Replication Teachers Guide Manual

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DNA can be mutated by a number of natural environmental and chemical sources. One of the
most potent natural mutagens is ultraviolet light. Most people are now aware of the potential for
ultraviolet light to cause mutations that result in skin cancer, and sunblocks are now used by most
sunbathers to prevent such mutational events. Ultraviolet light causes mutations because it may cause
neighboring nitrogen-containing bases in a single strand of DNA to bond together to form a single
molecule called a “diamer.” This diamerization results in a local distortion of the normal DNA
structure, causing replication and transcription enzymes to “stall” and make errors in these processes.
This results either in premature termination or in mismatching of nitrogen-containing base pairs on the
complementary DNA or RNA strand being formed. Replication errors may become permanent errors in
the genome because the “mutation” is then accurately copied during subsequent rounds of replication.
Chemicals in the environment can also cause mutagenic events by bonding or interacting with
specific nitrogen-containing bases of DNA, such that normal base-pairing is altered during replication.
Occasionally, whole sections of DNA may be deleted. Sometimes random segments of foreign DNA
may be inserted into the middle of a gene by events such as a “cross-over” in which two pieces of
double-stranded DNA exchange segments.
All cells have proteins that are specifically designed to seek out and remove altered sequences of DNA.
It is easy to imagine how altered DNA segments might be located by virtue of abnormal base pairing.
For example, an adenine positioned complementary to a guanine (instead of a thymine) would readily
stand out due to the abnormal base-pair length or bulk, as shown in Figure 1 below.
MODULE III: CODING, TRANSLATION, AND MUTATIONS
LESSON 7
Figure 1: (A) Normal adenine-thymine base-pair and (B) adenine-guanine mismatch representing a mutational event.
Notice the differences in overall base-pair diameters as well as the altered position and angle for connection to the
sugar-phosphate backbone (arrows).
When base mismatches occur, repair enzymes that exist in the cell must determine which of the
mismatched bases represents the un-mutated sequence and which represents the result of a mutation.
How can a cellular enzyme determine which is which? Most cells have a method for tagging a strand of
DNA after it is correctly formed and “proofread” so that when the new strand next becomes the parent
strand during subsequent replication, it is ignored and the new daughter strand becomes the target for
any repair mechanisms. The “tag” that cells put on DNA strands after proofreading is usually a series of
methyl groups added to certain nitrogen-containing bases; thus, “methylation” is the process that often
follows DNA replication.
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