APE1 role in DNA base excision repair (BER)

APE1 role in DNA base excision repair (BER). This figure gives a very general overview of the BER pathway and is discussed in more detail in other chapters in this review issue. A) Repair is initiated by a damage specific DNA glycosylase, which removes the damaged base to generate an AP site. Monofunctional DNA glycosylases remove the damaged base to generate an AP site (shown) whereas bifunctional glycosylases in addition to excising the damaged base also nick the phosphodiester backbone, 3′ to the AP site (not shown). APE1 processes the AP sites by hydrolyzing the backbone 5′ to the AP site to generate 3′OH and 5′ dRP groups. The 5′ dRP group is removed by the dRPase function of DNA Polymerase β and it also fills in the correct base. Repair is completed by DNA Ligase III/XRCC1 by sealing the nick. Failure to repair such accumulated AP sites leads to cytotoxicity, increased apoptosis. Elevated levels of APE1 in cancer cells have been linked to resistance to chemotherapy, poor prognosis and survival. Thus inhibiting APE1 leads to sensitization of cancer cells to chemotherapeutic agents [].B) In the major short-patch (SP) BER pathway regular AP sites are repaired by the removal of the single damaged base. Modified or oxidized AP sites are repaired by the long-patch (LP) BER pathway where a flap of 3–8 nucleotides is displaced and excised by Fen1. DNA polymerase β, δ or ε then inserts the correct nucleotides and repair is completed by sealing of the nick by DNA ligase I. APE1 also interacts with PCNA in the LP BER pathway [].

Publication

APE1/Ref-1 Role in Redox Signaling: Translational Applications of Targeting the Redox Function of the DNA Repair/Redox Protein APE1/Ref-1. () Mark R. Kelley, et al. Curr Mol Pharmacol. ;5(1):36-53. Figure: F3. All organisms Drosophila melanogaster Homo sapiens

Disease mentions