Molecular Biology Of The Cell 6th Edition by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter

Exercise 11

0 PolyADP-ribose polymerase (PARP) plays a key role in the repair of DNA single-strand breaks. In the pres- ence of the PARP inhibitor olaparib, single-strand breaks accumulate. When a replication fork encounters a sin- gle-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 recom- bination, however, inhibition of PARP triggers cell death. Patients who have only one functional copy of the Brca1 gene, which is required for homologous recombina- tion, 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 olapari b. Explain how it is that treatment with olaparib kills the cancer cells in these patients, but does not harm their normal cells.