Disease relevance of Apex1

• A putative O-sialoglycoprotease (a homologue of Pasteurella haemolytica glycoprotease, gcp; abbreviated as Prsmg1/Gcpl1) gene consisting of 11 exons and 10 introns spanning 7.3 kb lies immediately adjacent to the Apex gene in a 5'-to-5' orientation [1].
• On cDNA microarray analysis, in addition to apoptosis-related genes, genes associated with atrophy, APEX nuclease, MutS homologue (E. coli), testosterone-repressed-prostatic-message-2 (TRPM-2), connective tissue growth factor, collagen alpha 2 type V, and cell adhesion kinase were differentially expressed [2].

High impact information on Apex1

• The redox factor/AP endonuclease Ref-1 (APE, APEX, HAP1) affects both DNA repair and the activity of various transcription factors, and controls sensitivity to genotoxic insults [3].
• The upregulation of BER activities after IP was likely because of increased expression of repair enzymes beta-polymerase, AP endonuclease, and OGG1 [4].
• Two genes involved in DNA repair and cell cycle control, APEN (apurinic endonuclease) and GADD45 (growth arrest and DNA damage 45) were upregulated [5].
• In the present study a significant increase in the level of uracil in liver DNA as early as 3 weeks after initiation of folate/methyl deficiency was accompanied by parallel increases in DNA strand breaks, AP sites and increased levels of AP endonuclease mRNA [6].
• After conversion of the 3'-phosphate into a 3'-OH group by the chromatin 3'-phosphatase, there will be the same one-nucleotide gap, limited by 3'-OH and 5'-phosphate, as that formed by the successive actions of the AP endonuclease and the beta-elimination catalyst in the first pathway [7].

Biological context of Apex1

• Genomic sequencing and chromosomal assignment of the gene encoding rat APEX nuclease, a multifunctional DNA repair enzyme, were performed [1].
• DNA affinity-precipitation analyses showed that Ref-1/Ape was part of the multiprotein transcriptional complex forming on a 64-mer sequence encompassing a minimal hypoxic response element [8].
• The active Apex gene consists of 5 exons and 4 introns spanning 2.1 kb [1].
• An active Apex gene and a processed pseudogene were isolated from a rat genomic library [1].
• The Apex gene locus was mapped to rat chromosome 15p12 using in situ hybridization [1].

Anatomical context of Apex1

• Ref-1/Ape is critical for formation of the hypoxia-inducible transcriptional complex on the hypoxic response element of the rat pulmonary artery endothelial cell VEGF gene [8].
• The AP endonuclease receptors are likely to be on the cytosolic side of the endoplasmic reticulum [9].
• Interestingly, the mitochondrial activities of initiators for base excision repair (BER), the bifunctional glycosylase/AP lyases as well as AP endonuclease, were significantly higher in cerebellar granule cells compared with astrocytes [10].
• All the binding sites on the microsomes appear to have the same affinity for the AP endonuclease, suggesting the presence of receptors for the enzyme [9].
• The rat-liver microsomal AP endonuclease. The endoplasmic reticulum is presented as a net thrown into the cytosol to capture newly synthesized karyophilic proteins [9].

Associations of Apex1 with chemical compounds

• The separation was performed on a Apex ODS column in the isocratic mode using a mobile phase composed of 22.5% acetonitrile, 77.5% Sorensen phosphate buffer (pH 7.0), and 0.30 mL of tetrabutylammonium phosphate reagent (Pic A) [11].
• The increased mitochondrial AP endonuclease activity in combination with decreased polymerase gamma activity may cause an imbalance in oxidative BER leading to an increased production and persistence of mtDNA damage in neurons when treated with menadione [10].
• Granule cells exhibited a significantly higher intracellular oxidative state compared with primary astrocytes as well as increases in reductants, such as glutathione, and redox sensitive signaling molecules, such as AP endonuclease/redox effector factor-1 [10].

Other interactions of Apex1

• The co-transcription factor and DNA repair enzyme, Redox effector factor-1/apurinic/apyrimidinic endonuclease (Ref-1/Ape), facilitates DNA binding and transcriptional activity of a number of transactivating factors, including those governing hypoxia-induced gene expression HIF-1 [8].
• The putative promoter region of the Apex gene lacks the typical TATA box, but contains CAAT boxes and a CpG island having putative binding sites for several transcription factors, such as Sp1, AP-2, GATA-1 and ATF [1].
• 0. Catalase and AP endonuclease 1, which have been known as peroxisomal and nuclear, respectively, have shown a ratio of PM:CM>1.0, confirming the reports about their mitochondrial location [12].

Analytical, diagnostic and therapeutic context of Apex1

• Co-immunoprecipitation experiments indicated that Ref-1/Ape present in nuclear extract interacted with HIF-1 and p300 but not ATF/CREB [8].
• Electrophoretic mobility shift assays failed to detect direct DNA binding of Ref-1/Ape to either the HIF-1 or AP1 DNA recognition sequences present in the hypoxic response element of the VEGF gene [8].
• The HPLC analysis employed a symmetrical or standard reversed-phase HPLC column (Apex ODS, 5 microm, 25 cm x 0.46 cm) for blood or urine analysis, a mobile phase of water methanol acetonitrile (40:30:30) containing 20 microl 100 ml(-1) diethylamine at a flow rate of 1 ml min(-1), and UV detection at 254 nm [13].

References