PolyADP-ribose polymerase (PARP) plays a keyrole in the repair of DNA single-strand breaks. In the pres-ence of the PARP inhibitor olaparib, single-strand breaksaccumulate. 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 homologousrecombination. In cells defective for homologous recom-bination, however, inhibition of PARP triggers cell death.Patients who have only one functional copy of theBrca1 gene, which is required for homologous recombina-tion, are at much higher risk for cancer of the breast andovary. Cancers that arise in these tissues in these patientscan be treated successfully with olaparib. Explain how it isthat treatment with olaparib kills the cancer cells in thesepatients, but does not harm their normal cells.
Gene Interactions
When the expression of a single trait is influenced by two or more different non-allelic genes, it is termed as genetic interaction. According to Mendel's law of inheritance, each gene functions in its own way and does not depend on the function of another gene, i.e., a single gene controls each of seven characteristics considered, but the complex contribution of many different genes determine many traits of an organism.
Gene Expression
Gene expression is a process by which the instructions present in deoxyribonucleic acid (DNA) are converted into useful molecules such as proteins, and functional messenger ribonucleic (mRNA) molecules in the case of non-protein-coding genes.
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 olaparib. Explain how it is
that treatment with olaparib kills the cancer cells in these
patients, but does not harm their normal cells.
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