POLA1 - DNA polymerase alpha catalytic subunit - human protein (Function)
 
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POLA1 »  DNA polymerase alpha catalytic subunit   [ EC 2.7.7.7 ]
 
Protein also known as:  DNA polymerase alpha catalytic subunit p180.
Gene name:  POLA1
Family name: DNA polymerase type-B
Entry whose protein(s) existence is based on evidence at protein level
extend overview
1 72 1
GENE REF ISO

Function

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Overview 
Plays an essential role in the initiation of DNA replication. During the S phase of the cell cycle, the DNA polymerase alpha complex (composed of a catalytic subunit POLA1/p180, a regulatory subunit POLA2/p70 and two primase subunits PRIM1/p49 and PRIM2/p58) is recruited to DNA at the replicative forks via direct interactions with MCM10 and WDHD1. The primase subunit of the polymerase alpha complex initiates DNA synthesis by oligomerising short RNA primers on both leading and lagging strands. 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. The reason this transfer occurs is because the polymerase alpha has limited processivity and lacks intrinsic 3' exonuclease activity for proofreading error, and therefore is not well suited for replicating long complexes.  
1
  • CuratedUniProtKB
GO molecular function 
3'-5' exonuclease activitydefinition[GO:0008408] silver  
  • IBARefGenome
4 iron, 4 sulfur cluster bindingdefinition[GO:0051539]  
  • IEAUniProtKB KW
Chromatin bindingdefinition[GO:0003682]  
1
  • IDAUniProtKB
DNA bindingdefinition[GO:0003677]  
2
  • IDAUniProtKB
Contributes to DNA primase activitydefinition[GO:0003896]  
1
  • IDAUniProtKB
DNA-directed DNA polymerase activitydefinition[GO:0003887]  
3
  • IDAUniProtKB
Metal ion bindingdefinition[GO:0046872]  
  • IEAUniProtKB KW
Nucleoside bindingdefinition[GO:0001882] silver  
  • IEAInterPro 2 GO
Nucleotide bindingdefinition[GO:0000166]  
1
  • IDAUniProtKB
Protein bindingdefinition[GO:0005515]  
11
  • IPIIntAct
  • IPIUniProtKB
Protein heterodimerization activitydefinition[GO:0046982] silver  
  • IEAOrtholog Compara
GO biological process 
Cell proliferationdefinition[GO:0008283]  
1
  • IDAUniProtKB
Not  DNA repairdefinition[GO:0006281]  
1
  • IDAUniProtKB
DNA replicationdefinition[GO:0006260]  
3
  • IMPUniProtKB
DNA replication initiationdefinition[GO:0006270]  
1
  • IDAUniProtKB
DNA replication, synthesis of RNA primerdefinition[GO:0006269]  
1
  • IDAGOC
DNA strand elongation involved in DNA replicationdefinition[GO:0006271]  
1
  • IMPUniProtKB
Not  DNA synthesis involved in DNA repairdefinition[GO:0000731]  
2
  • IMPUniProtKB
Double-strand break repair via nonhomologous end joiningdefinition[GO:0006303]  
1
  • IMPUniProtKB
Lagging strand elongationdefinition[GO:0006273]  
2
  • IDAUniProtKB
Leading strand elongationdefinition[GO:0006272]  
2
  • IDAUniProtKB
Mitotic S phasedefinition[GO:0000084]  
1
  • IDAUniProtKB
Nucleic acid phosphodiester bond hydrolysisdefinition[GO:0090305] silver  
  • IBARefGenome
Not  Nucleotide-excision repair, DNA gap fillingdefinition[GO:0006297] silver  
  • IBARefGenome
Translesion synthesisdefinition[GO:0019985] silver  
  • IBARefGenome
Viral processdefinition[GO:0016032]  
  • IEAUniProtKB KW
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 2.7.7.7: Deoxynucleoside triphosphate + DNA(n) diphosphate + DNA(n+1).  
  • CuratedUniProtKB
It requires the following cofactor
Binds 1 4Fe-4S cluster (By similarity).  
  • CuratedUniProtKB
Pathways 
According to KEGG, this protein belongs to the following pathways:
DNA replication  hsa03030+5422  
Metabolic pathways  hsa01100+5422  
Purine metabolism  hsa00230+5422  
Pyrimidine metabolism  hsa00240+5422  
According to Reactome, this protein belongs to the following pathways:
Activation of the pre-replicative complex  REACT_1095  
DNA replication initiation  REACT_2244  
E2F mediated regulation of DNA replication  REACT_471  
G1/S-Specific Transcription  REACT_683  
Inhibition of replication initiation of damaged DNA by RB1/E2F1  REACT_329  
Leading Strand Synthesis  REACT_1838  
Polymerase switching  REACT_1792  
Polymerase switching on the C-strand of the telomere  REACT_7987  
Processive synthesis on the lagging strand  REACT_1385  
Removal of the Flap Intermediate  REACT_70  
Telomere C-strand synthesis initiation  REACT_7993  
Note 
In eukaryotes there are five DNA polymerases: alpha, beta, gamma, delta, and epsilon which are responsible for different reactions of DNA synthesis.  
  • CuratedUniProtKB
 

Keywords

Biological process 
DNA replication  definition   [KW-0235]
Host-virus interaction  definition   [KW-0945]
Molecular function 
DNA-directed DNA polymerase  definition   [KW-0239]
Nucleotidyltransferase  definition   [KW-0548]
Transferase  definition   [KW-0808]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links