Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

CHAPTER 20 END-OF-CHAPTER PROBLEMS
1143
20–10 PolyADP-ribose polymerase (PARP) plays a key
role in the repair of DNA single-strand breaks. In the presence
of the PARP inhibitor olaparib, single-strand breaks
accumulate. When a replication fork encounters a single-strand
break, it converts it to a double-strand break,
which in normal cells is then repaired by homologous
recombination. In cells defective for homologous recombination,
however, inhibition of PARP triggers cell death.
Patients who have only one functional copy of the
Brca1 gene, which is required for homologous recombination,
are at much higher risk for cancer of the breast and
ovary. Cancers that arise in these tissues in these patients
can be treated successfully with olaparib. Explain how it is
that treatment with olaparib kills the cancer cells in these
patients, but does not harm their normal cells.
20–11 The Tasmanian devil, a carnivorous Australian
marsupial, is threatened with extinction by the spread
of a fatal disease in which a malignant oral–facial tumor
interferes with the animal’s ability to feed. You have been
called in to analyze the source of this unusual cancer. It
seems clear to you that the cancer is somehow spread from
devil to devil, very likely by their frequent fighting, which
is accompanied by biting around the face and mouth. To
uncover the source of the cancer, you isolate tumors from
11 devils captured in widely separated regions and examine
them. As might be expected, the karyotypes of the
tumor cells are highly rearranged relative to that of the
wild-type devil (Figure Q20–3). Surprisingly, you find that
the karyotypes from all 11 tumor samples are very similar.
Moreover, one of the Tasmanian devils has an inversion on
chromosome 5 that is not present in its facial tumor. How
do you suppose this cancer is transmitted from devil to
devil? Is it likely to arise as a consequence of an infection
by a virus or microorganism? Explain your reasoning.
(A)
(B)
(C)
Tasmanian devil (Sarcophilus harrisii)
1 2 3 4 5 6
1 3 4 5 6 M1 M2 M3 M4
Figure Q20–3 Karyotypes of cells from Tasmanian devils (Problem
20–11). (A) A Tasmanian devil. (B) Normal karyotype for a male
Tasmanian devil. The karyotype has 14 chromosomes, including XY.
(C) Karyotype of cancer cells found in each of the 11 facial tumors
studied. The karyotype has 13 chromosomes, no sex chromosomes,
no chromosome 2 pair, one chromosome 6, two chromosomes 1 with
deleted long arms, and four highly rearranged marker chromosomes
(M1–M4). (A, reproduced courtesy of Museum Victoria; B and C, from
A.M. Pearse and K. Swift, Nature 439:549, 2006. With permission from
Macmillan Publishers Ltd.)
XY
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