Small‐molecule Inhibitors of DNA Base Excision Repair

Abstract

Abstract Cells rely on several DNA ( deoxyribonucleic acid ) repair pathways to maintain the integrity of their genetic information, including DNA base excision repair (BER). BER involves the removal of a DNA base, damaged in some way by a chemical modification, and then subsequent repair to reconstitute the DNA. Inhibition of the proteins and enzymes that mediate BER can result in cell death, especially in actively dividing cells. As such, many of these enzymes are targets for pharmaceutical research to combat cancer and severe inflammatory ailments. Small molecules have been identified that inhibit at least three of the principal enzymes of BER: an enzyme that participates in the signalling of DNA damage, an endonuclease involved in processing an intermediate of BER and a DNA polymerase . This article focuses on the known BER enzyme inhibitors, many of which are pharmaceutical candidates in clinical trials to treat disease. Key concepts: Several small molecules have been developed that inhibit the enzymes involved in DNA base excision repair. Inhibition of DNA base excision repair can sensitize cells to DNA‐damaging treatments. Inhibitors of the DNA base excision repair enzymes are being investigated as potential treatments for cancer and severe inflammation.