AP endonuclease

Apurinic/apyrimidinic (AP) endonuclease is an enzyme that is involved in the DNA base excision repair pathway (BER).

Its main role in the repair of damaged or mismatched nucleotides in DNA is to create a nick in the phosphodiester backbone of the AP site created when DNA glycosylase removes the damaged base.

[1] The APE1 enzyme creates a nick in the phosphodiester backbone at an abasic (baseless) site through a simple acyl substitution mechanism.

Next, electrons from one of the oxygen atom in the phosphate group moves down, kicking off one of the other oxygen to create a free 5´ phosphate group on the AP site and a free 3´-OH on the normal nucleotide, both of which are stabilized by the Mg2+ ion.

Because APE1 performs an essential function in DNA base-excision repair pathway, it has become a target for researchers looking for means to prevent cancer cells from surviving chemotherapy.

Not only is APE1 needed in and of itself to create the nick in the DNA backbone so that the enzymes involved later in the BER pathway can recognize the AP-site, it also has a redox function that helps activate other enzymes involved in DNA repair.

Molecular graphics images were produced using the UCSF Chimera package from the Resource for Biocomputing, Visualization, and Informatics at the University of California, San Francisco (supported by NIH P41 RR-01081).

Ribbon diagram of APE1. PDB = 1de9. [ 1 ]
Positive residues on the surface of the APE1 protein (in blue) anchor and bend DNA though interactions with DNA's negative phosphate groups. PDB 1de9. [ 1 ]
Hydrogen bonding among key amino acid residues help stabilize active site structure. Moreover, a negatively charged residue (Glu 96) helps hold the Mg2+ also needed to stabilize the AP site in place PDB 1de9. [ 1 ]
Mechanism illustrated
Lucanthone