Disease relevance of APN2

• Expression of ETH1 in a dut-1 xthA3 Escherichia coli strain demonstrated that the gene product functionally complements the missing AP endonuclease activity [1].
• Transformation of apn1 eth1 cells with an expression vector containing ETH1 reversed the hypersensitivity to MMS and limited the rate of spontaneous mutagenesis [1].

High impact information on APN2

• Apn2 also has an AP endonuclease activity and functions in the removal of abasic sites from DNA [2].
• Importantly, PCNA stimulates the 3'-->5' exonuclease and 3'-phosphodiesterase activities of Apn2 [2].
• Consistent with these biochemical observations, genetic studies indicate the involvement of APN2 in the repair of H(2)O(2)-induced DNA damage in a pathway alternate to APN1, and the Ala59 mutation inactivates this function of Apn2 [3].
• Here, we show that purified yeast Apn2 protein contains 3'-phosphodiesterase and 3'-->5' exonuclease activities, and mutation of the active-site residue Glu59 to Ala in Apn2 inactivates both these activities [3].
• An open reading frame was found to encode a putative protein (34% identical to the Schizosaccharomyces pombe eth1(+) [open reading frame SPBC3D6.10] gene product) with a 347-residue segment homologous to the exonuclease III family of AP endonucleases [1].

Biological context of APN2

• In this study, we investigated the function of these two enzymes in base excision repair (BER) for methyl methanesulfonate (MMS) damage using the nth1 and apn2 mutants [4].
• The phenotype of apn2 degrees uve1 degrees double mutants indicates that these genes define distinct spontaneous mutation avoidance pathways [5].

Associations of APN2 with chemical compounds

• Synthesis of mRNA from ETH1 in wild-type cells was induced sixfold relative to that in untreated cells after exposure to the alkylating agent methyl methanesulfonate (MMS) [1].
• Elimination of ETH1 in apn1 strains also increased spontaneous mutation rates 9- or 31-fold compared to the wild type as determined by reversion to adenine or lysine prototrophy, respectively [1].
• This species difference was due to the absence of delta-lyase activity in S. cerevisiae, since expression of bacterial Fpg conferred Tpp1-dependent resistance to methylmethane sulfonate in yeast lacking the abasic endonucleases Apn1 and Apn2 [6].
• While uve1 degrees cells show only a modest sensitivity to the oxidizing agent hydrogen peroxide (H(2)O(2)), both uve1 degrees and apn2 degrees cells also display a marked increased in mutation rate following exposure to H(2)O(2) doses [5].
• Overexpression of Apn2p in nth1 mutants failed to suppress MMS sensitivity [7].

Other interactions of APN2

• Stimulation of 3'-->5' exonuclease and 3'-phosphodiesterase activities of yeast apn2 by proliferating cell nuclear antigen [2].
• Roles of base excision repair enzymes Nth1p and Apn2p from Schizosaccharomyces pombe in processing alkylation and oxidative DNA damage [7].

References