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7.4 What Mutations Tell Us About Gene Structure 239

Figure 7.20 Skin lesions in a xeroderma pigmentosum self- appointed “biology watcher” Lewis Thomas acknowl-
patient. This heritable disease is caused by the lack of a critical edges that changes in DNA are behind the phenotypic vari-
enzyme in the nucleotide excision repair system. ations that are the raw material on which natural selection
© Barcroft Media/Getty Images has acted for billions of years to drive evolution.
As Dr. Thomas’ poetic line suggests, the necessity
for mutation is fundamental: Without mutations, life
would have died out long ago because it could not have
responded to changes in the environment. DNA repair pro-
cesses must therefore walk a fine line. They must be effi-
cient enough to protect genomes from the huge number of
assaults on DNA that are always occurring, but the propa-
gation of life requires some mutations to be transmitted to
future generations.

essential concepts
• Cells have many different enzyme systems that minimize
mutations by repairing DNA damage or replication errors.
• Double-strand breaks, which are particularly dangerous to
genomes, can be repaired through homologous
recombination (HR) or nonhomologous end-joining (NHEJ).
• Correction of DNA replication errors requires mismatch
repair systems to choose the correct strand to change.
Bacteria accomplish this task by marking parental strands
with methyl groups.
• If normal repair mechanisms are overwhelmed by too
much DNA damage, cells can then mobilize error-prone
DNA repair systems.
• Mutations in genes specifying proteins that participate in
DNA repair often lead to human diseases, including cancer.
• Mutations are the raw material of evolution. Although
are homozygous for mutations in any one of seven genes many mutations are harmful, rare mutations may confer a
encoding enzymes that normally function in this repair sys- selective advantage.
tem. As a result, the thymine dimers caused by ultraviolet
light cannot be removed efficiently. Unless these people avoid
all exposure to sunlight, their skin cells begin to accumulate
mutations that eventually lead to skin cancer (Fig. 7.20). 7.4 What Mutations Tell Us
In another example, researchers have recently learned
that hereditary forms of colorectal cancer in humans are About Gene Structure
associated with mutations in human genes that are closely
related to the E. coli genes encoding the mismatch-repair
proteins MutS and MutL. In yet another example, the breast learning objectives
cancer genes BRCA1 and BRCA2 (mutation of either of 1. Describe complementation testing and how its results
which is associated with a high risk of breast cancer in distinguish mutations in a single gene from mutations in
women) encode proteins that function in double-strand different genes.
break repair via homologous recombination. Chapter 20 2. Explain how Benzer’s experimental results revealed that
discusses the fascinating connections between DNA repair the rII region in bacteriophage T4 contains two genes,
and cancer in more detail. each composed of many nucleotide pairs.
3. Discuss how Benzer used deletions to map mutations in
the rII region.
DNA Repair Cannot Be 100% Efficient
“The capacity to blunder slightly is the real marvel of
DNA. Without this special attribute, we would still The science of genetics depends absolutely on mutations,
be anaerobic bacteria and there would be no music.” In because we can track genes in crosses only through the
these two sentences, the eminent medical scientist and phenotypic effects of their mutant variants. In the 1950s