The function of endonuclease III is to repair DNA by removing numerous forms of modified thymine and cytosine bases (11).  As stated in the introduction endonuclease III has both a DNA N-glycosylase activity and an apurinic/apyrimidinic (AP) lyase activity.  The N-glycosylase activity cleaves a variety of ring damaged, ring rearranged, and ring contracted pyrimidines (9).  Thymine is the most susceptible base to become damaged due to the nature and accessibility of the C(5)-C(6) double bond.  N-glycosylase activity releases these damaged thymine residues (7).  The AP lyase activity incises the DNA sugar-phosphate backbone 3' to the abasic or baseless site.  Further processing by endonucleases, DNA polymerase, and DNA ligase complete the DNA repair (7).
            The phosphodiester bond of the DNA backbone is not cleaved by classic phosphodiesterase activity, which will leave behind a 3'-OH or a base free deoxyribose at the 3' end.  The DNA backbone is actually cleaved by a beta-elimination.  The beta-elimination leaves a 3'-terminal unsaturated sugar and a product with a terminal 5'-phosphate.  Therefore, E. coli 'endonuclease III' is not an endonuclease (2).
            The endonuclease III enzyme contains an [4Fe-4S] cluster.  The reactions catalyzed by endonuclease III are clearly not those traditionally associated with Fe-S clusters.  The redox properties of the Fe-S cluster make a redox role extremely remote.  No catalytic role for the Fe-S cluster is found.  The only change that occurs in the cluster is consistent with a protein confirmation change that disturbs the orientation of one or more ligating cysteine residues.  Therefore, the Fe-S cluster must have a structural or regulatory role.  When the [4Fe-4S] cluster was taken out of endonuclease III, there was no enzyme activity or DNA binding activity and endonuclease III denatured.  This suggests the the Fe-S cluster plays a structural role in endonuclease III (5).
            When endonuclease III repairs closely opposed base sites, the removal of the first damaged base and complete restoration of the DNA must occur before the second site can be repaired.  This is done in order to avoid a double-stranded break.  A single-stranded break is made during the removal of the first damaged base, which generates a pseudo single-stranded structure around the second damaged base due to local melting of the DNA.  So the endonuclease III enzyme is unable to act on the second damaged base because endonuclease III only binds and repairs double-stranded DNA.  Even though glycosylate activity is inhibited by a closely positioned break in the opposite strand, the AP lyase activity is not (3).
            The endonuclease III enzyme has the function of DNA repair.  There are many things that are not yet known about how this enzyme works.  However, studies have shown that frequently occurring damaged thymine bases need to be cleaved and repaired (7), the AP site is cleaved via the beta-elimination reaction (2), the [4Fe-4S] cluster has a structural and DNA binding role (5), and that glycosylate activity is inhibited by a closely positioned break in the opposite strand (3).  More information will be found on the function of E. coli endonuclease III as research continues.

Table of Contents
Structure

[Introduction][Active Site][DNA Interactions][References]