Protein: DNA polymerase alpha catalytic subunit (EC 2.7.7.7) (DNA polymerase alpha catalytic subunit p180) (P33609)
Organism: Mus musculus (Mouse)
Function: 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. During the S phase of the cell cycle, the DNA polymerase alpha complex (composed of a catalytic subunit POLA1, a regulatory subunit POLA2 and two primase subunits PRIM1 and PRIM2) 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. In the cytosol, responsible for a substantial proportion of the physiological concentration of cytosolic RNA:DNA hybrids, which are necessary to prevent spontaneous activation of type I interferon responses.
Subcellular location: Nucleus {ECO:0000250|UniProtKB:P09884}. Cytoplasm, cytosol {ECO:0000250|UniProtKB:P09884}. Note=In the cytosol, colocalizes with RNA:DNA hybrids with a speckled pattern. {ECO:0000250|UniProtKB:P09884}.
Interaction partners:
- DNA polymerase alpha subunit B
- WD repeat and HMG-box DNA-binding protein 1
- DNA primase large subunit
- DNA primase small subunit
- DNA polymerase epsilon catalytic subunit A
- DNA polymerase epsilon subunit 2
- DNA polymerase delta subunit 2
- DNA polymerase delta catalytic subunit
- DNA replication licensing factor MCM4
- DNA replication licensing factor MCM2
Sequence:
MAPMHEEDCKLEASAVSDSGSFAASRARREKKSKKGRQEALERLKKAKAGEKYKYEVEDLTSVYEEVDEEQYSKLVQARQDDDWIVDDDGIGYVEDGREIFDDDLEDDALDTCGKGSDGKAHRKDRKDVKKPSVTKPNNIKAMFIASAGKKTTDKAVDLSKDDLLGDILQDLNTETAQITPPPVLIPKKKRSTGALLNPFSVHTPKAIPSGKPASPVLRNEPLLTPIPLKRAELAGELAQPECPEDEQELGVMEFEDGDFDESMDTEKVDEKPVTAKTWDQETEPVERVEHEADPERGTTSYLENFLPDVSCWDIDQDDESIPQEVQVDSSNLPLVKGADDEQVFQFYWLDAYEDPYNQPGVVFLFGKVWIESVKTHVSCCVMVKNIERTLYFLPREMKFDLNTGKETAIPVTMKDVYEEFDSKISAKYKIMKFKSKIVEKNYAFEIPDVPEKSEYLEVRYSAEVPQLPQNLKGETFSHVFGTNTSSLELFLMNRKIKGPCWLEVKNPQLLNQPISWCKFEVMALKPDLVNVIKDVSPPPLVVMSFSMKTMQNVQNHQHEIIAMAALVHHSFALDKAPPEPPFQTHFCVVSKPKDCIFPCDFKEVISKKNMKVEIAATERTLIGFFLAKVHKIDPDILVGHNICSFELEVLLQRINECKVPYWSKIGRLRRSNMPKLGSRSGFGERNATCGRMICDVEISAKELIHCKSYHLSELVQQILKTERIVIPTENIRNMYSESSYLLYLLEHIWKDARFILQIMCELNVLPLALQITNIAGNIMSRTLMGGRSERNEFLLLHAFYENNYIVPDKQIFRKPQQKLGDEDEEIDGDTNKYKKGRKKATYAGGLVLDPKVGFYDKFILLLDFNSLYPSIIQEFNICFTTVQRVTSEVQKATEDEEQEQIPELPDPNLEMGILPREIRKLVERRKQVKQLMKQQDLNPDLVLQYDIRQKALKLTANSMYGCLGFSYSRFYAKPLAALVTYKGREILMHTKDMVQKMNLEVIYGDTDSIMINTNSTNLEEVFKLGNKVKSEVNKLYKLLEIDIDAVFKSLLLLKKKKYAALVVEPTSDGNYITKQELKGLDIVRRDWCDLAKDTGNFVIGQILSDQSRDTIVENIQKRLIEIGENVLNGSVPVSQFEINKALTKDPQDYPDRKSLPHVHVALWINSQGGRKVKAGDTVSYVICQDGSNLTATQRAYAPEQLQKLDNLAIDTQYYLAQQIHPVVARICEPIDGIDAVLIALWLGLDSTQFRVHQYHKDEENDALLGGPAQLTDEEKYKDCEKFKCLCPSCGTENIYDNVFEGSGLDMEPSLYRCSNVDCKVSPLTFMVQLSNKLIMDIRRCIKKYYDGWLICEEPTCCSRLRRLPLHFSRNGPLCPVCMKAVLRPEYSDKSLYTQLCFYRYIFDADCALEKLTEHEKDKLKKQFFPLRVLQDYRKVKNIAEQFLSWSGYSEVNLSKLFANYAGKS