Accepted_test

Structures of many polypeptides possess intrinsically disordered regions, which may be important for protein–protein and enzyme–substrate interactions, protein intracellular localization, etc. A number of such proteins may be found in base excision repair (BER), a pathway that purges our genome of most lesions generated in DNA by spontaneous and induced oxidation, deamination, alkylation, and base loss. However, the roles of the disordered regions in these proteins are mostly unknown. Here we show that disordered regions in DNA glycosylases and AP endonucleases, the enzymes that catalyze the first two steps of the BER pathway, are involved in non-specific DNA binding, discrimination of damaged vs undamaged bases, and regulation of enzyme activity. Unlike truly intrinsically disordered regions, many of them likely populate a limited number of distinct conformations, which could have specific functional roles.