FB2024_02 , released April 23, 2024
Gene: Dmel\PolA1
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General Information
Symbol
Dmel\PolA1
Species
D. melanogaster
Name
DNA polymerase alpha subunit 1
Annotation Symbol
CG6349
Feature Type
FlyBase ID
FBgn0259113
Gene Model Status
Stock Availability
Enzyme Name (EC)
DNA-directed DNA polymerase (2.7.7.7)
Gene Summary
DNA polymerase alpha subunit 1 (PolA1) encodes the catalytic subunit of DNA polymerase alpha, responsible for initial synthesis on the leading strand and on each Okazaki fragment of the lagging strand. [Date last reviewed: 2019-09-26] (FlyBase Gene Snapshot)
Also Known As

DNApol-alpha180, DNA polymerase α, DNApol-α, DNApol-α180, POLA

Key Links
Genomic Location
Cytogenetic map
Sequence location
Recombination map
3-73
RefSeq locus
NT_033777 REGION:21666562..21671750
Sequence
Genomic Maps
Other Genome Views
The following external sites may use different assemblies or annotations than FlyBase.
Function
Gene Ontology (GO) Annotations (17 terms)
Molecular Function (9 terms)
Terms Based on Experimental Evidence (4 terms)
CV Term
Evidence
References
Terms Based on Predictions or Assertions (6 terms)
CV Term
Evidence
References
inferred from biological aspect of ancestor with PANTHER:PTN000035348
enables DNA binding
inferred from electronic annotation with InterPro:IPR006134
inferred from biological aspect of ancestor with PANTHER:PTN000035348
inferred from biological aspect of ancestor with PANTHER:PTN000035348
Biological Process (6 terms)
Terms Based on Experimental Evidence (2 terms)
CV Term
Evidence
References
Terms Based on Predictions or Assertions (4 terms)
CV Term
Evidence
References
involved_in DNA replication
inferred from electronic annotation with InterPro:IPR015088
inferred from biological aspect of ancestor with PANTHER:PTN000035348
inferred from biological aspect of ancestor with PANTHER:PTN000035348
inferred from biological aspect of ancestor with PANTHER:PTN000035348
inferred from electronic annotation with InterPro:IPR045846
Cellular Component (2 terms)
Terms Based on Experimental Evidence (2 terms)
CV Term
Evidence
References
Terms Based on Predictions or Assertions (1 term)
CV Term
Evidence
References
Protein Family (UniProt)
Belongs to the DNA polymerase type-B family. (P26019)
Catalytic Activity (EC/Rhea)
DNA-directed DNA polymerase activity
a 2'-deoxyribonucleoside 5'-triphosphate + DNA(n) = diphosphate + DNA(n+1) (2.7.7.7)
Summaries
Gene Snapshot
DNA polymerase alpha subunit 1 (PolA1) encodes the catalytic subunit of DNA polymerase alpha, responsible for initial synthesis on the leading strand and on each Okazaki fragment of the lagging strand. [Date last reviewed: 2019-09-26]
Gene Group (FlyBase)
DNA POLYMERASE ALPHA-PRIMASE -
DNA polymerase alpha-primase synthesizes short RNA-DNA primers on the lagging strand during DNA synthesis. It is a heterotetramer composed of two polymerase subunits (DNApol-α180 and DNApol-α73) and two primase subunits (DNApol-α50 and DNApol-α60). DNApol-α180 and DNApol-α50 encode the DNA polymerase and RNA primase catalytic activities, respectively, while DNApol-α73 and DNApol-α60 encode the regulatory subunits. (Adapted from PMID:30005324.)
DNA POLYMERASE CATALYTIC SUBUNITS -
Multiple DNA polymerases are required for DNA replication and/or repair in eukaryotic cells. The alpha-primase, delta, epsilon, zeta and gamma polymerases exist as multi-subunit complexes in which one of the subunits has catalytic activity, whereas other DNA polymerases act as single molecules. (Adapted from PMID:30005324.)
3'-5' DNA EXONUCLEASES -
3'-5'-exodeoxyribonucleases catalyze the sequential degradation of double-stranded DNA acting progressively in a 3'-to-5' direction, releasing nucleoside 5'-phosphates.
Protein Function (UniProtKB)
Catalytic subunit of the DNA polymerase alpha complex (also known as the alpha DNA polymerase-primase complex) which plays an essential role in the initiation of DNA synthesis (PubMed:9858578, PubMed:6773966, PubMed:6806812, PubMed:6403945, PubMed:6409898). During the S phase of the cell cycle, the DNA polymerase alpha complex (composed of a catalytic subunit PolA1, an accessory subunit PolA2 and two primase subunits, the catalytic subunit Prim1 and the regulatory subunit Prim2) is recruited to DNA at the replicative forks (PubMed:9858578, PubMed:6773966, PubMed:6806812, PubMed:6409898). The primase subunit of the polymerase alpha complex initiates DNA synthesis by oligomerising short RNA primers on both leading and lagging strands (By similarity). These primers are initially extended by the polymerase alpha catalytic subunit and subsequently transferred to polymerase delta and polymerase epsilon for processive synthesis on the lagging and leading strand, respectively (By similarity). In addition to polymerase activity, exhibits 3' to 5' exonuclease activity (PubMed:3112771, PubMed:3129427).
(UniProt, P26019)
Gene Model and Products
Number of Transcripts
1
Number of Unique Polypeptides
1

Please see the JBrowse view of Dmel\PolA1 for information on other features

To submit a correction to a gene model please use the Contact FlyBase form

Protein Domains (via Pfam)
Isoform displayed:
Pfam protein domains
InterPro name
classification
start
end
Protein Domains (via SMART)
Isoform displayed:
SMART protein domains
InterPro name
classification
start
end
Structure
Protein 3D structure   (Predicted by AlphaFold)   (AlphaFold entry P26019)

If you don't see a structure in the viewer, refresh your browser.
Model Confidence:
  • Very high (pLDDT > 90)
  • Confident (90 > pLDDT > 70)
  • Low (70 > pLDDT > 50)
  • Very low (pLDDT < 50)

AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Some regions with low pLDDT may be unstructured in isolation.

Experimentally Determined Structures
Crossreferences
Comments on Gene Model

Gene model reviewed during 5.47

Sequence Ontology: Class of Gene
Transcript Data
Annotated Transcripts
Name
FlyBase ID
RefSeq ID
Length (nt)
Assoc. CDS (aa)
FBtr0084115
4624
1488
Additional Transcript Data and Comments
Reported size (kB)

4.8 (northern blot)

5.7 (northern blot)

Comments
External Data
Crossreferences
Polypeptide Data
Annotated Polypeptides
Name
FlyBase ID
Predicted MW (kDa)
Length (aa)
Theoretical pI
UniProt
RefSeq ID
GenBank
FBpp0083514
169.9
1488
8.11
Polypeptides with Identical Sequences

There is only one protein coding transcript and one polypeptide associated with this gene

Additional Polypeptide Data and Comments
Reported size (kDa)

1490 (aa); 180 (kD)

1505 (aa); 171 (kD)

Comments
External Data
Subunit Structure (UniProtKB)

Component of the alpha DNA polymerase complex (also known as the alpha DNA polymerase-primase complex) consisting of four subunits: the catalytic subunit PolA1, the regulatory subunit PolA2, and the primase complex subunits Prim1 and Prim2 respectively (PubMed:6773966, PubMed:6403945, PubMed:6409898, PubMed:7592543). PolA1 associates with the DNA primase complex before association with PolA2 (PubMed:6409898). Interacts with Dpit47; the interaction inhibits the activity of the DNA polymerase and occurs only in proliferating cells but not in quiescent cells (PubMed:11493638).

(UniProt, P26019)
Post Translational Modification

In embryos, a cleaved form of 130 kDa is produced up to cycle 14 and then disappears.

(UniProt, P26019)
Domain

The CysA-type zinc finger is required for PCNA-binding.

(UniProt, P26019)
Linkouts
Sequences Consistent with the Gene Model
Mapped Features

Click to get a list of regulatory features (enhancers, TFBS, etc.) and gene disruptions (point mutations, indels, etc.) within or overlapping Dmel\PolA1 using the Feature Mapper tool.

External Data
Crossreferences
Eukaryotic Promoter Database - A collection of databases of experimentally validated promoters for selected model organisms.
Linkouts
Expression Data
Testis-specificity index

The testis specificity index was calculated from modENCODE tissue expression data by Vedelek et al., 2018 to indicate the degree of testis enrichment compared to other tissues. Scores range from -2.52 (underrepresented) to 5.2 (very high testis bias).

-0.31

Transcript Expression
in situ
Stage
Tissue/Position (including subcellular localization)
Reference
northern blot
Stage
Tissue/Position (including subcellular localization)
Reference
Additional Descriptive Data
Marker for
 
Subcellular Localization
CV Term
Polypeptide Expression
No Assay Recorded
Stage
Tissue/Position (including subcellular localization)
Reference
immunolocalization
Stage
Tissue/Position (including subcellular localization)
Reference
western blot
Stage
Tissue/Position (including subcellular localization)
Reference
Additional Descriptive Data

PolA1 protein is observed in nuclei of nurse cells and follicle cells. During early stages of embryogenesis, PolA1 protein is mainly nuclear although dispersal occurrs during mitotic phases of the cell cycle.

DNApol-α180 activity is highest in embryos, 2nd instar larvae, and adult females.

Marker for
 
Subcellular Localization
CV Term
Evidence
References
Expression Deduced from Reporters
High-Throughput Expression Data
Associated Tools

JBrowse - Visual display of RNA-Seq signals

View Dmel\PolA1 in JBrowse
RNA-Seq by Region - Search RNA-Seq expression levels by exon or genomic region
Reference
See Gelbart and Emmert, 2013 for analysis details and data files for all genes.
Developmental Proteome: Life Cycle
Developmental Proteome: Embryogenesis
External Data and Images
Linkouts
DRscDB - A single-cell RNA-seq resource for data mining and data comparison across species
EMBL-EBI Single Cell Expression Atlas - Single cell expression across species
FlyAtlas2 - A Drosophila melanogaster expression atlas with RNA-Seq, miRNA-Seq and sex-specific data
Fly-FISH - A database of Drosophila embryo and larvae mRNA localization patterns
Flygut - An atlas of the Drosophila adult midgut
Images
Alleles, Insertions, Transgenic Constructs, and Aberrations
Classical and Insertion Alleles ( 7 )
For All Classical and Insertion Alleles Show
 
Other relevant insertions
Transgenic Constructs ( 7 )
For All Alleles Carried on Transgenic Constructs Show
Transgenic constructs containing/affecting coding region of PolA1
Transgenic constructs containing regulatory region of PolA1
Aberrations (Deficiencies and Duplications) ( 1 )
Inferred from experimentation ( 1 )
Gene disrupted in
Inferred from location ( 0 )
Variants
Variant Molecular Consequences
Alleles Representing Disease-Implicated Variants
Phenotypes
Orthologs
Human Orthologs (via DIOPT v9.1)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
Homo sapiens (Human) (4)
14 of 14
Yes
Yes
2 of 14
No
No
2 of 14
No
No
1 of 14
No
No
Model Organism Orthologs (via DIOPT v9.1)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
Rattus norvegicus (Norway rat) (4)
14 of 14
Yes
Yes
2 of 14
No
No
2 of 14
No
No
1 of 14
No
No
Mus musculus (laboratory mouse) (4)
13 of 14
Yes
Yes
2 of 14
No
No
2 of 14
No
No
1 of 14
No
No
Xenopus tropicalis (Western clawed frog) (2)
11 of 13
Yes
Yes
1 of 13
No
No
Danio rerio (Zebrafish) (4)
14 of 14
Yes
Yes
2 of 14
No
No
2 of 14
No
No
1 of 14
No
No
Caenorhabditis elegans (Nematode, roundworm) (4)
13 of 14
Yes
Yes
2 of 14
No
No
2 of 14
No
No
1 of 14
No
No
Anopheles gambiae (African malaria mosquito) (4)
12 of 12
Yes
Yes
Arabidopsis thaliana (thale-cress) (6)
13 of 13
Yes
Yes
2 of 13
No
No
2 of 13
No
No
2 of 13
No
No
1 of 13
No
No
1 of 13
No
No
Saccharomyces cerevisiae (Brewer's yeast) (4)
13 of 13
Yes
Yes
2 of 13
No
No
2 of 13
No
No
2 of 13
No
No
Schizosaccharomyces pombe (Fission yeast) (4)
12 of 12
Yes
Yes
2 of 12
No
No
2 of 12
No
No
2 of 12
No
No
Escherichia coli (enterobacterium) (1)
5 of 11
Yes
No
Other Organism Orthologs (via OrthoDB)
Data provided directly from OrthoDB:PolA1. Refer to their site for version information.
Paralogs
Paralogs (via DIOPT v9.1)
Drosophila melanogaster (Fruit fly) (3)
5 of 13
3 of 13
1 of 13
Human Disease Associations
FlyBase Human Disease Model Reports
    Disease Ontology (DO) Annotations
    Models Based on Experimental Evidence ( 0 )
    Allele
    Disease
    Evidence
    References
    Potential Models Based on Orthology ( 2 )
    Modifiers Based on Experimental Evidence ( 0 )
    Allele
    Disease
    Interaction
    References
    Disease Associations of Human Orthologs (via DIOPT v9.1 and OMIM)
    Note that ortholog calls supported by only 1 or 2 algorithms (DIOPT score < 3) are not shown.
    Functional Complementation Data
    Functional complementation data is computed by FlyBase using a combination of the orthology data obtained from DIOPT and OrthoDB and the allele-level genetic interaction data curated from the literature.
    Interactions
    Summary of Physical Interactions
    Summary of Genetic Interactions
    esyN Network Diagram
    Show/hide secondary interactors 
    (data from AllianceMine provided by esyN)
    esyN Network Key:
    Suppression
    Enhancement
    Other Interaction Browsers

    Please look at the allele data for full details of the genetic interactions
    Starting gene(s)
    Interaction type
    Interacting gene(s)
    Reference
    Starting gene(s)
    Interaction type
    Interacting gene(s)
    Reference
    External Data
    Subunit Structure (UniProtKB)
    Component of the alpha DNA polymerase complex (also known as the alpha DNA polymerase-primase complex) consisting of four subunits: the catalytic subunit PolA1, the regulatory subunit PolA2, and the primase complex subunits Prim1 and Prim2 respectively (PubMed:6773966, PubMed:6403945, PubMed:6409898, PubMed:7592543). PolA1 associates with the DNA primase complex before association with PolA2 (PubMed:6409898). Interacts with Dpit47; the interaction inhibits the activity of the DNA polymerase and occurs only in proliferating cells but not in quiescent cells (PubMed:11493638).
    (UniProt, P26019 )
    Linkouts
    BioGRID - A database of protein and genetic interactions.
    DroID - A comprehensive database of gene and protein interactions.
    MIST (genetic) - An integrated Molecular Interaction Database
    MIST (protein-protein) - An integrated Molecular Interaction Database
    Pathways
    Signaling Pathways (FlyBase)
    Metabolic Pathways
    External Data
    Linkouts
    KEGG Pathways - A collection of manually drawn pathway maps representing knowledge of molecular interaction, reaction and relation networks.
    Genomic Location and Detailed Mapping Data
    Chromosome (arm)
    3R
    Recombination map
    3-73
    Cytogenetic map
    Sequence location
    FlyBase Computed Cytological Location
    Cytogenetic map
    Evidence for location
    93F2-93F2
    Limits computationally determined from genome sequence between P{PZ}InR05545 and P{PZ}tsl00617
    Experimentally Determined Cytological Location
    Cytogenetic map
    Notes
    References
    Mapped by recombination and deficiency analysis.
    93F1-93F1
    (determined by in situ hybridisation)
    Experimentally Determined Recombination Data
    Location
    Left of (cM)
    Right of (cM)
    Notes
    Stocks and Reagents
    Stocks (11)
    Genomic Clones (19)
    cDNA Clones (17)
     

    Please Note This section lists cDNAs and ESTs that fall within the genomic extent of the gene model, which may include cDNAs and ESTs of genes within introns, or of overlapping genes. Please see JBrowse for alignment of the cDNAs and ESTs to the gene model.

    cDNA clones, fully sequenced
    BDGP DGC clones
    Other clones
      Drosophila Genomics Resource Center cDNA clones

      For each fully sequenced cDNA the DGRC maintains various forms of the cDNA (e.g tagged or untagged) in several different host vectors for subsequent cloning and expression in Drosophila and Drosophila cell lines.

      cDNA Clones, End Sequenced (ESTs)
      BDGP DGC clones
      RNAi and Array Information
      Linkouts
      DRSC - Results frm RNAi screens
      Antibody Information
      Laboratory Generated Antibodies
       

      polyclonal

      Commercially Available Antibodies
       
      Cell Line Information
      Publicly Available Cell Lines
       
        Other Stable Cell Lines
         
          Other Comments

          Reducing DNApol-α180 levels by itself des not result in any defects, while reducing DNApol-α180 levels in the absence of mei-41 results in elevated p53-dependent apoptosis, rough eyes and increased genomic instability.

          In vitro binding studies of E2f and Dp to the DNApol-α180 promoter region reveals each of the E2f binding sites plays a distinct role as positive or negative element in the regulation of the DNApol-α180 promoter during development.

          A specific polyclonal antibody stains interphase nuclei and the surrounding cytoplasmic regions. The protein is present in the embryo as a maternal product. The 130kD proteolytic product is also present in embryos as a maternal product; unlike the 180kD protein this decreases in amount after cycle 10 and is not detectable after cycle 14.

          Subunits of DNA polymerase α and δ are purified from embryos and characterised.

          Expression pattern and subcellular distribution of the protein during development is studied using antibodies.

          DNApol-α180 is negatively regulated by zen protein. This repression is mediated by the DRE (DNA replication-related element) sites in the DNApol-α180 promoter. The amount of Dref is reduced in transfected Kc cells expressing zen, suggesting that zen represses expression of DNA replication-related genes by reducing the amount of Dref.

          The properties of the DNA polymerase α enzyme have been studied.

          DNApol-α and mus209 products share DRE, an 8bp palindrome required for high expression.

          Immunoaffinity-purified DNA polymerase α-primase includes not only the 180kD protein, but also 145, 140 and 130kD proteins, due to proteolytic cleavage of the 180kD protein at F130/S131, T180/S181 and F237/S238.

          Embryonic DNA polymerase α complex, isolated by immunological techniques, contains a protein kinase activity. The kinase will phosphorylate His1, but prefers peptides contained in the DNA polymerase α kinase complex.

          Mono Q anion exchange chromatography used to resolve DNA polymerase activities in 0-2.5hr embryos. DNApol-δ and DNApol-α distinguished by copurification with DNAprimase (DNApol-α) or 3'-5'exonuclease activity (DNApol-δ), immunoblot analysis with DNApol-α specific antibodies, sensitivity to aphidicolin (both DNApol-α and DNApol-δ sensitive) and BuPdGTP (DNApol-α more sensitive), and processivity measurements with and without PCNA (DNApol-δ has PCNA-inducible high processivity).

          Recognition and binding of synthetic template-primers by DNA-polymerase-α holoenzyme studied: at least 4 base pair complementarity is required for efficient binding and incorporation. Results suggest that there are intrinsic aspects to the mechanism of nucleotide incorporation which ensure fidelity of DNA synthesis and may provide insight into mechanism of polymerase translocation along templates.

          The nucleotide sequence of DNA polymerase α gene was determined. Expression of the enzyme is closely related to cell proliferation during development.

          25bp DNA oligomer containing m4T is used in a gel extension assay to measure the efficiency of incorporation of dATP and dGTP opposite m4T using a DNA polymerase α-primase complex. The DNA polymerase α shows a clear preference for pairing with dGTP.

          Relationship to Other Genes
          Source for database merge of

          Source for merge of: DNApol-α180 E(mus304)

          Additional comments
          Nomenclature History
          Source for database identify of

          Source for identity of: PolA1 DNApol-α180

          Nomenclature comments
          Etymology
          Synonyms and Secondary IDs (54)
          Reported As
          Symbol Synonym
          183 kDa pol α
          DNA Pol-α180
          DNA pol α
          DNA polymerase α 180 kD
          DNApolα180
          Pol-α180
          Polα 180KDa
          Name Synonyms
          180 kDa subunit
          180 kDa subunit of DNA polymerase α
          180 kDa subunit of polymerase-primase
          DNA polymerase Alpha 180 kD
          DNA polymerase alpha
          DNA polymerase alpha 180kD
          DNA polymerase alpha 180kD subunit
          DNA polymerase alpha subunit 1
          DNA polymerase α 148,000 α subunit
          DNA polymerase α 180-kDa subunit
          DNA polymerase α 180kD
          DNA polymerase α 182,000 α subunit
          DNA polymerase-primase 180 kda subunit
          DNA polymerase-α p180 subunit
          DNA-polymerase α
          DNApol-alpha180
          Enhancer of mus304
          Secondary FlyBase IDs
          • FBgn0004493
          • FBgn0010016
          • FBgn0041636
          Datasets (0)
          Study focus (0)
          Experimental Role
          Project
          Project Type
          Title
          Study result (0)
          Result
          Result Type
          Title
          External Crossreferences and Linkouts ( 53 )
          Sequence Crossreferences
          NCBI Gene - Gene integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes, and links to genome-, phenotype-, and locus-specific resources worldwide.
          GenBank Nucleotide - A collection of sequences from several sources, including GenBank, RefSeq, TPA, and PDB.
          GenBank Protein - A collection of sequences from several sources, including translations from annotated coding regions in GenBank, RefSeq and TPA, as well as records from SwissProt, PIR, PRF, and PDB.
          RefSeq - A comprehensive, integrated, non-redundant, well-annotated set of reference sequences including genomic, transcript, and protein.
          UniProt/GCRP - The gene-centric reference proteome (GCRP) provides a 1:1 mapping between genes and UniProt accessions in which a single 'canonical' isoform represents the product(s) of each protein-coding gene.
          UniProt/Swiss-Prot - Manually annotated and reviewed records of protein sequence and functional information
          Other crossreferences
          AlphaFold DB - AlphaFold provides open access to protein structure predictions for the human proteome and other key proteins of interest, to accelerate scientific research.
          DRscDB - A single-cell RNA-seq resource for data mining and data comparison across species
          EMBL-EBI Single Cell Expression Atlas - Single cell expression across species
          FlyAtlas2 - A Drosophila melanogaster expression atlas with RNA-Seq, miRNA-Seq and sex-specific data
          KEGG Genes - Molecular building blocks of life in the genomic space.
          MARRVEL_MODEL - MARRVEL (model organism gene)
          Linkouts
          BioGRID - A database of protein and genetic interactions.
          Drosophila Genomics Resource Center - Drosophila Genomics Resource Center (DGRC) cDNA clones
          DroID - A comprehensive database of gene and protein interactions.
          DRSC - Results frm RNAi screens
          Eukaryotic Promoter Database - A collection of databases of experimentally validated promoters for selected model organisms.
          FlyCyc Genes - Genes from a BioCyc PGDB for Dmel
          Fly-FISH - A database of Drosophila embryo and larvae mRNA localization patterns
          Flygut - An atlas of the Drosophila adult midgut
          FlyMet - A comprehensive tissue-specific metabolomics resource for Drosophila.
          KEGG Pathways - A collection of manually drawn pathway maps representing knowledge of molecular interaction, reaction and relation networks.
          MIST (genetic) - An integrated Molecular Interaction Database
          MIST (protein-protein) - An integrated Molecular Interaction Database
          References (138)