Research progress of human AP endonuclease 1: structure, catalytic mechanism and inhibitors

The high stability of phosphodiester bonds is considered to be one of the important reasons for the genetic role of nucleic acids, and their cleavage is also the core of many key biochemical processes, including DNA replication/ repair, and RNA processing/ degradation. As an important part of the base excision repair (BER) pathway, human apurinic/ apyrimidinic endonuclease 1 (APE1) is indispensable for the repair of abasic sites and other DNA damage, including ionizing radiation, DNA covalently bonding induced by cytotoxic antitumor drugs, etc. For tumor cells, the DNA repair activity of APE1 may lead to the occurrence of radiotherapy and chemotherapy resistance. The overexpression of APE1 often poses a serious threat to the effectiveness of tumor treatment, indicating a longer time, a much larger dose, less effective chemotherapy, and poor prognosis. It is of great urgency to design novel APE1 inhibitors. Rational design and modification of inhibitor molecules are closely related to the research progress of both structural biology and catalytic mechanism. In this review, the structure, catalytic mechanism, inhibitors, and other important biochemical information regarding APE1 are summarized, which will help in the design and modification of drug molecules targeting APE1.