POLA: 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. Belongs to the DNA polymerase type-B family.
Protein type: DNA repair, damage; DNA replication; EC 2.7.7.7; Nuclear envelope; Nucleotide Metabolism - purine; Nucleotide Metabolism - pyrimidine; Transferase
Chromosomal Location of Human Ortholog: Xq22
Cellular Component: alpha DNA polymerase:primase complex; chromatin; cytosol; nuclear envelope; nuclear matrix; nucleolus; nucleoplasm; nucleus
Molecular Function: 3'-5' exonuclease activity; 4 iron, 4 sulfur cluster binding; chromatin binding; DNA binding; DNA-directed DNA polymerase activity; double-stranded DNA binding; metal ion binding; nucleic acid binding; nucleoside binding; nucleotide binding; protein heterodimerization activity; protein kinase binding; purine nucleotide binding; pyrimidine nucleotide binding
Biological Process: cell proliferation; DNA repair; DNA replication; DNA replication initiation; DNA replication, synthesis of RNA primer; DNA strand elongation involved in DNA replication; DNA synthesis involved in DNA repair; double-strand break repair via nonhomologous end joining; lagging strand elongation; leading strand elongation
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