CLINICAL CASES
109
[11.2]
B. Since
BRCA1
is inherited in an autosomal dominant fashion, then
one allele is sufficient to produce the
BRCA1
protein. However, if the
normal allele is somatically mutated or deleted, then the affected cell
cannot produce the
BRCA1
protein and can be transformed into a
tumor cell.
[11.3]
D.
BRCA1
plays a significant role in the repair of double-strand breaks,
therefore, since homologous recombination requires a cleavage of both
strands of a DNA molecule, this event is most likely to be affected by
a deficiency in this protein. Thymine dimers, mismatches, and adducts
of DNA with carcinogens are effectively removed by a process of exci-
sion repair, in which a section of one strand of DNA is removed.
B IO C H E M IS T R Y PE A R L S
DNA replication normally occurs during the S phase of the cell
cycle.
DNA replication occurs in a semiconservative fashion and this is
because of the intrinsic antiparallel nature of the double helix.
All known DNA polymerases synthesize DNA in a 5' to 3' direction.
To respond to the various forms of DNA damage, cells have evolved
a host of DNA repair mechanisms that serve to restore the genetic
code.
Tumor suppressors refer to a general class of proteins that function
to slow and alter cell growth and development through a variety
of mechanisms.
BRCA
tumor suppressor gene when mutated,
increases the risk of breast cancer.
Inactivation of
BRCA1,
a gene that appears to operate in DNA repair
pathways that appear generic to various cell types, predisposes
women to inherited forms of breast cancer, but the exact mecha-
nism has been elusive.
REFERENCES
Couch FJ, Weber BL. Breast cancer. In: Scriver CR, Beaudet AL, Sly WS, et al.,
eds. The Metabolic and Molecular Basis of Inherited Disease, 8th ed. New York:
McGraw-Hill, 2001:999-1031.
Edenberg HJ. DNA replication, recombination, and repair. In: Devlin TM, ed.
Textbook of Biochemistry with Clinical Correlations, 5th ed. New York: Wiley-
Liss, 2002.
Scully R Chen J, Ochs RL. Dynamic changes of BRCA1 subnuclear location and
phosphorylation state are initiated by DNA damage. Cell 1997;90:425-35.
Scully R, Livingston DM. In search of the tumor-suppressor functions of BRCA1
and BRCA2. Nature 2000;408:429-32.
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