An AP (apurinic/apyrimidinic) site, also known as an abasic site, is a region of DNA that is lacking a purine or pyrimidine base. This can occur spontaneously, or as a result of DNA damage. When DNA damage occurs, DNA repair pathways are activated. These pathways are highly conserved and are critical for maintaining genome integrity, however they are potential targets for cancer therapy since up-regulation of DNA repair mechanisms is a major means by which cancer cells can overcome the effects of chemotherapeutic and radiotherapeutic treatments (1). The majority of cancer treatments exert their effects by damaging DNA, which results in the impairment of cell signaling and subsequent cell death. By knocking down or inhibiting proteins involved in DNA repair, tumor cell sensitivity to DNA-damaging therapeutics could be significantly increased, thereby enhancing the efficacy of cancer treatments.
A number of DNA repair pathways are known, including base excision repair, nucleotide excision repair, double-strand break repair and mismatch repair pathways (2). Human apurinic/apyrimidinic endonuclease 1 / redox effector factor 1 (APE1 / Ref1) plays a pivotal role in the base excision repair (BER) pathway. During the first step of this pathway, DNA glycosylases recognize and remove damaged nucleotide bases to form AP sites; in the second step of the pathway APE1 creates a nick in the DNA sugar-phosphate backbone at these sites, enabling the damage to be recognized by other enzymes involved in DNA repair. In addition to creating the nick in the DNA, APE1 also has a redox function which activates the enzymes that are required to repair the damage (3).
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Western Blot: APE1 Antibody
Based on the method of base excision, AP endonucleases can be classified into two groups. APE1 is a class II AP endonuclease and its expression is pre-dominantly nuclear, however there is evidence to suggest that expression levels and sub-cellular localization are altered in tumors (4). There is strong rationale for targeting APE1 with chemotherapeutic agents; elevated levels of Ape1 have been linked to chemoresistance, cells which lack APE1 are non-viable, and APE1 knockdown can sensitize cancer cells to chemotherapeutics. Work is ongoing to establish whether it is more beneficial to block the repair or redox functions of APE1, or to block both functions simultaneously, when developing therapeutic agents for cancer (3).
Novus Biologicals offers various APE1 reagents for your research needs including:
Written by Emma Easthope
