Disease relevance of DNApol-alpha180

• The patterns of kinetic pause sites observed for Escherichia coli DNA polymerase III holoenzyme is qualitatively similar to that found for DNA polymerase alpha [1].
• The stimulatory activity of mouse AAF is highly specific for DNA polymerase alpha/primase; no effect was observed with mouse DNA polymerases beta, gamma, or delta, nor with retroviral, bacteriophage, or bacterial DNA polymerases [2].
• Drosophila DNA polymerase alpha, HIV-1, and AMV reverse transcriptases had "little" difficulty inserting opposite abasic lesions, with efficiencies comparable to misinsertions opposite normal template bases [3].

High impact information on DNApol-alpha180

• The 120-kDa polypeptide can be distinguished from the large subunit of Drosophila DNA polymerase alpha on the basis of the peptides generated by partial cleavage with N-chlorosuccinimide and by its failure to react with a monoclonal antibody directed against the large subunit of DNA polymerase alpha [4].
• The kinetics of elongating primer termini are measured with purified Drosophila DNA polymerase alpha [5].
• DNA polymerase alpha mutants from a Drosophila melanogaster cell line [6].
• Specification of regions of DNA replication initiation during embryogenesis in the 65-kilobase DNApolalpha-dE2F locus of Drosophila melanogaster [7].
• In the DNA polymerase alpha gene (DNApolalpha) locus, where an initiation region, oriDalpha, had been identified in cultured Kc cells, repression of origin activity in the coding region was detected after formation of cellular blastoderms, and the range of the initiation region had become confined by 5 h after fertilization [7].

Chemical compound and disease context of DNApol-alpha180

• The capacity of the large fragment of DNA polymerase I from Escherichia coli and of DNA polymerase alpha from Drosophila embryo to replicate single-stranded M13mp10 DNA containing either purine or pyrimidine monoadducts was compared [8].

Biological context of DNApol-alpha180

• Distinct roles of E2F recognition sites as positive or negative elements in regulation of the DNA polymerase alpha 180 kDa catalytic subunit gene promoter during Drosophila development [9].
• Three DREs and one DRE are present in the DNA polymerase alpha gene (nucleotides-217, -83, and -30 with respect to the transcription initiation site) and in the PCNA gene (nucleotide-100), respectively [10].
• The Drosophila melanogaster gene and cDNA which span the entire open reading frame for DNA polymerase alpha, were cloned, and their nucleotide sequences were determined [11].
• The amino acid sequence of the polypeptide was 37% homologous with that of the catalytic subunit of human DNA polymerase alpha [11].
• Results obtained using various deletion derivatives of the promoter region and chemically synthesized oligonucleotides of the DNA replication-related element (DRE), a positive cis-acting element found in both DNA polymerase alpha and PCNA genes, revealed that the DRE sequences are responsible to repression by Zen protein [12].

Anatomical context of DNApol-alpha180

• Ectopic expression of the N-terminal fragment in salivary gland cells reduced the contents of mRNAs for the 180-kDa subunit of DNA polymerase alpha and for dE2F and the extent of DNA endoreplication [13].
• Levels of the DNA polymerase alpha mRNA were high in unfertilized eggs and early embryos, relatively high in adult female flies and second-instar larva, and low in bodies at other stages of development [11].
• Error rates for conventionally purified DNA polymerase-alpha from calf thymus, chicken, and human sources have been reported to be one in 10,000 to one in 40,000 nucleotides incorporated [14].
• We have confirmed that the DNA replication-related element (DRE) consisting of an 8-bp palindrome, TATCGATA, and not neighboring sequences, are responsible for activating promoters of the Drosophila melanogaster (Dm) PCNA (proliferating cell nuclear antigen)- and DNA polymerase alpha-encoding genes in both cultured cell and transgenic fly systems [15].

Associations of DNApol-alpha180 with chemical compounds

• The deoxynucleoside triphosphate analogs N2-(p-butylphenyl)deoxyguanosine triphosphate and N2-(p-butylphenyl)deoxyadenosine triphosphate are potent inhibitors of DNA polymerase alpha [16].
• We confirmed this mechanism for the DNA polymerase alpha holoenzyme purified from Drosophila melanogaster embryos and studied the interaction of Drosophila pol alpha with synthetic oligonucleotide template-primers containing modified tetrahydrofuran moieties as model abasic lesions chemically engineered at a number of defined sites [17].
• A polyacrylamide gel assay is used to measure the kinetics of adding a single deoxyribonucleotide onto either a correctly matched or mismatched primer 3' terminus (on M13 template) for all possible DNA base pairs and mispairs using Drosophila melanogaster DNA polymerase alpha (Pol alpha) and avian myeloblastosis virus reverse transcriptase [18].
• The DNA polymerase and primase activities of the intact DNA polymerase alpha from early embryos of Drosophila melanogaster co-sediment in native glycerol gradients [19].
• The expression of the zen resulted in reduction of the abundance of mRNA for the transfected chloramphenicol acetyltransferase gene and also mRNAs for both DNA polymerase alpha and PCNA [12].

Regulatory relationships of DNApol-alpha180

• D-SSB stimulates the extent and processivity of DNA synthesis of its cognate DNA polymerase alpha [20].

Other interactions of DNApol-alpha180

• Novel 8-base pair sequence (Drosophila DNA replication-related element) and specific binding factor involved in the expression of Drosophila genes for DNA polymerase alpha and proliferating cell nuclear antigen [10].
• DNase I footprinting analysis indicated that DREF binds to the 24-bp DRE region of the DNA polymerase alpha gene in which 8-bp palindromic sequences are centered [10].
• DNA replication-related element (DRE) and the DRE-binding factor (DREF) play an important role in regulating DNA replication-related genes such as PCNA and DNA polymerase alpha in Drosophila [21].

Analytical, diagnostic and therapeutic context of DNApol-alpha180

• There was no reaction in an immunological test using monoclonal antibody against Drosophila DNA polymerase alpha [22].
• The interaction with the DNA polymerase alpha is not related to the special situation in early embryos where there are large amounts of maternal protein stockpiles of the polymerase, as it occurs to the same level in early and late embryos and also in proliferating cell culture [23].

References