What Are Subunits Of Dna

Protein-coding factor in the species Human sapiens

POLA1

Bachelor structures

PDB

Ortholog search: PDBe RCSB

List of PDB id codes
1K0P, 1K18, 1N5G, 4Q5V, 4QCL, 4Y97, 5EXR, 5IUD

Identifiers

Aliases

POLA1, NSX, POLA, p180, Polymerase (DNA directed), alpha 1, polymerase (DNA) alpha i, catalytic subunit, Deoxyribonucleic acid polymerase alpha 1, catalytic subunit, VEODS

External IDs

OMIM: 312040 MGI: 99660 HomoloGene: 6802 GeneCards: POLA1

Factor location (Human)

Chr.	X chromosome (man)^[1]

Band	Xp22.11-p21.3	Starting time	24,693,873 bp^[1]
Band	Xp22.11-p21.3	End	24,996,986 bp^[1]

Factor location (Mouse)

Chr.	Ten chromosome (mouse)^[2]

Band	X C3\|10 41.06 cM	Showtime	92,348,373 bp^[2]
Band	X C3\|10 41.06 cM	End	92,675,761 bp^[2]

RNA expression pattern

Bgee

Man

Mouse (ortholog)

Summit expressed in

sural nervus

Achilles tendon

oocyte

ganglionic eminence

secondary oocyte

bone marrow cells

corpus callosum

gastrocnemius muscle

thymus

popliteal artery

Top expressed in

morula

ureter

blastocyst

intestinal wall

dermis

secondary oocyte

vas deferens

Paneth prison cell

mitt

maxillary prominence

More than reference expression data

BioGPS


More than reference expression data

Gene ontology
Molecular function	transferase activity iv iron, 4 sulfur cluster bounden nucleotidyltransferase activity nucleoside binding iron-sulfur cluster binding chromatin binding metal ion binding protein binding nucleic acrid binding poly peptide kinase binding Deoxyribonucleic acid-directed Dna polymerase activity nucleotide binding DNA binding DNA replication origin binding purine nucleotide binding protein heterodimerization action unmarried-stranded DNA binding pyrimidine nucleotide bounden
Cellular component	nuclear envelope nuclear matrix nucleolus chromatin nucleoplasm nucleus cytoplasm cytosol alpha Deoxyribonucleic acid polymerase:primase complex
Biological process	DNA synthesis involved in Dna repair lagging strand elongation regulation of transcription involved in G1/S transition of mitotic prison cell cycle Dna replication leading strand elongation cell population proliferation viral process double-strand break repair via nonhomologous end joining DNA strand elongation involved in Dna replication DNA replication, synthesis of RNA primer telomere maintenance via semi-conservative replication G1/S transition of mitotic cell bicycle DNA replication initiation Dna repair nucleotide-excision repair Deoxyribonucleic acid synthesis involved in UV-impairment excision repair mitotic DNA replication initiation synthesis of RNA primer involved in mitotic DNA replication
Sources:Amigo / QuickGO

Orthologs

Species

Human

Mouse

Entrez


5422


18968

Ensembl


ENSG00000101868


ENSMUSG00000006678

UniProt


P09884


P33609

RefSeq (mRNA)


NM_016937 NM_001330360 NM_001378303


NM_008892

RefSeq (protein)


NP_001317289 NP_058633 NP_001365232


NP_032918

Location (UCSC)

Chr 10: 24.69 – 25 Mb

Chr X: 92.35 – 92.68 Mb

PubMed search

^[3]

^[iv]

Wikidata

View/Edit Human

View/Edit Mouse

Dna polymerase alpha catalytic subunit is an enzyme that in humans is encoded by the POLA1 gene.^[5]

Shared primase-bounden peptide in archaeal PolD and eukaryotic Polα^[vi]

Function [edit]

This cistron encodes the p180 catalytic subunit of DNA polymerase α-primase. Political leader α has express processivity and lacks 3′ exonuclease activity for proofreading errors. Thus it is not well suited to efficiently and accurately copy long templates (unlike Pol Delta and Epsilon). Instead information technology plays a more limited role in replication. Pol α is responsible for the initiation of Dna replication at origins of replication (on both the leading and lagging strands) and during synthesis of Okazaki fragments on the lagging strand. The Pol α complex (pol α-Dna primase circuitous) consists of 4 subunits: the catalytic subunit POLA1, the regulatory subunit POLA2, and the small and the large primase subunits PRIM1 and PRIM2 respectively. One time primase has created the RNA primer, Politico α starts replication elongating the primer with ~20 nucleotides.

Clinical significance [edit]

In improver to its function during DNA replication, POLA1 plays a role in type I interferon activation. The POLA1 gene was plant to be the site of a mutation resulting in X-linked reticulate pigmentary disorder (XLPDR), OMIM 301220). This leads to altered mRNA splicing and decreased expression of POLA1 protein to a level that does not impair Dna replication. The reduction in POLA1 expression is accompanied past marked reduction in cytosolic RNA:Deoxyribonucleic acid hybrid molecules and a concomitant hyperactivation of the IRF3 pathway, with consequent overproduction of type I interferons.^[7]

Moreover, POLA1 deficiency, typical for XLPDR, also impair direct cytotoxicity of NK cells. POLA1 inhibition or a natural deficiency (XLPDR) affects the way the lytic granules secreted toward target cells. Equally a consequence, NK cells in XLPDR patients display functional deficiency. Interestingly, the POLA1 deficiency typical for XLPDR is not associated with whatever genomic damages or prison cell bike abort.^[eight] ^[9]

While the XLPDR mutation is resided in intron 13th, other somatic mutations in POLA1 were also described. Somatic mutation are associated with more profound deficiency of POLA1, with develops into X-linked intellectual inability (XLID). In a case of non-XLPDR mutations, beside of type I interferon signature patients too brandish mild to medium signs of intellectual disability, cell cycle arrest, proportionate short stature, microcephaly and hypogonadism.^[x]

Interactions [edit]

Deoxyribonucleic acid dependent polymerase alpha (Politico α) has been shown to collaborate with MCM4 and GINS1,^[viii] Retinoblastoma poly peptide,^[11] PARP1^[12] ^[13] and RBMS1.^[fourteen]

References [edit]

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000101868 - Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000006678 - Ensembl, May 2017
^ "Human PubMed Reference:". National Eye for Biotechnology Data, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Heart for Biotechnology Data, U.S. National Library of Medicine.
^ "Entrez Gene: POLA1 polymerase (Deoxyribonucleic acid directed), alpha i".
^ Madru C, Henneke G, Raia P, Hugonneau-Beaufet I, Pehau-Arnaudet Chiliad, England P, et al. (March 2020). "Structural basis for the increased processivity of D-family DNA polymerases in complex with PCNA". Nature Communications. eleven (i): 1591. Bibcode:2020NatCo..eleven.1591M. doi:10.1038/s41467-020-15392-9. PMC7101311. PMID 32221299.
^ Starokadomskyy P, Gemelli T, Rios JJ, Xing C, Wang RC, Li H, et al. (May 2016). "DNA polymerase-α regulates the activation of type I interferons through cytosolic RNA:Dna synthesis". Nature Immunology. 17 (v): 495–504. doi:x.1038/ni.3409. PMC4836962. PMID 27019227.
^ ^a ^b Starokadomskyy P, Wilton KM, Krzewski Yard, Lopez A, Sifuentes-Dominguez L, Overlee B, et al. (November 2019). "NK cell defects in 10-linked pigmentary reticulate disorder". JCI Insight. 4 (21). doi:x.1172/jci.insight.125688. PMC6948767. PMID 31672938.
^ Starokadomskyy P, Sifuentes-Dominguez L, Gemelli T, Zinn AR, Dossi MT, Mellado C, et al. (Nov 2017). "Evolution of the skin manifestations of Ten-linked pigmentary reticulate disorder". The British Journal of Dermatology. 177 (5): e200–e201. doi:ten.1111/bjd.15586. PMC5640471. PMID 28407217.
^ Van Esch H, Colnaghi R, Freson Grand, Starokadomskyy P, Zankl A, Backx L, et al. (May 2019). "Defective Deoxyribonucleic acid Polymerase α-Primase Leads to 10-Linked Intellectual Disability Associated with Severe Growth Retardation, Microcephaly, and Hypogonadism". American Periodical of Human being Genetics. 104 (5): 957–967. doi:ten.1016/j.ajhg.2019.03.006. PMC6506757. PMID 31006512.
^ Takemura M, Kitagawa T, Izuta S, Wasa J, Takai A, Akiyama T, Yoshida S (Nov 1997). "Phosphorylated retinoblastoma protein stimulates DNA polymerase blastoff". Oncogene. 15 (xx): 2483–2492. doi:10.1038/sj.onc.1201431. PMID 9395244.
^ Dantzer F, Nasheuer HP, Vonesch JL, de Murcia G, Ménissier-de Murcia J (April 1998). "Functional association of poly(ADP-ribose) polymerase with DNA polymerase blastoff-primase circuitous: a link between Deoxyribonucleic acid strand break detection and DNA replication". Nucleic Acids Enquiry. 26 (8): 1891–1898. doi:10.1093/nar/26.8.1891. PMC147507. PMID 9518481.
^ Simbulan CM, Suzuki M, Izuta S, Sakurai T, Savoysky Due east, Kojima 1000, et al. (Jan 1993). "Poly(ADP-ribose) polymerase stimulates Dna polymerase blastoff by physical association". The Journal of Biological Chemistry. 268 (1): 93–99. doi:10.1016/S0021-9258(18)54119-iii. PMID 8416979.
^ Niki T, Galli I, Ariga H, Iguchi-Ariga SM (June 2000). "MSSP, a poly peptide binding to an origin of replication in the c-myc cistron, interacts with a catalytic subunit of Deoxyribonucleic acid polymerase alpha and stimulates its polymerase activity". FEBS Letters. 475 (three): 209–212. doi:10.1016/S0014-5793(00)01679-3. PMID 10869558. S2CID 31594271.

External links [edit]

PDBe-KB provides an overview of all the structure data available in the PDB for Human Deoxyribonucleic acid polymerase alpha catalytic subunit

Farther reading [edit]

Pollok South, Stoepel J, Bauerschmidt C, Kremmer E, Nasheuer HP (Feb 2003). "Regulation of eukaryotic Dna replication at the initiation footstep". Biochemical Society Transactions. 31 (Pt ane): 266–269. doi:ten.1042/BST0310266. PMID 12546699.
Fisher PA, Korn D (September 1977). "Dna polymerase-alpha. Purification and structural characterization of the near homogeneous enzyme from homo KB cells". The Journal of Biological Chemistry. 252 (18): 6528–6535. doi:10.1016/S0021-9258(17)39990-8. PMID 893425.
Dornreiter I, Erdile LF, Gilbert IU, von Winkler D, Kelly TJ, Fanning E (Feb 1992). "Interaction of DNA polymerase alpha-primase with cellular replication protein A and SV40 T antigen". The EMBO Journal. 11 (2): 769–776. doi:10.1002/j.1460-2075.1992.tb05110.10. PMC556510. PMID 1311258.
Coverley D, Kenny MK, Lane DP, Wood RD (August 1992). "A role for the homo single-stranded Dna binding protein HSSB/RPA in an early stage of nucleotide excision repair". Nucleic Acids Research. 20 (15): 3873–3880. doi:10.1093/nar/20.xv.3873. PMC334061. PMID 1508673.
Popanda O, Thielmann HW (January 1992). "The function of DNA polymerases in Deoxyribonucleic acid repair synthesis of ultraviolet-irradiated human being fibroblasts". Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression. 1129 (ii): 155–160. doi:10.1016/0167-4781(92)90480-N. PMID 1730053.
Collins KL, Kelly TJ (April 1991). "Effects of T antigen and replication protein A on the initiation of DNA synthesis past Deoxyribonucleic acid polymerase blastoff-primase". Molecular and Cellular Biology. eleven (4): 2108–2115. doi:10.1128/mcb.11.4.2108. PMC359898. PMID 1848671.
Martelli AM, Cocco L, Manzoli FA (February 1991). "On the association of Dna polymerase alpha action with the nuclear matrix in HeLa cells". Cell Biology International Reports. 15 (2): 131–140. doi:10.1016/0309-1651(91)90104-Q. PMID 1903085.
Pearson Be, Nasheuer HP, Wang TS (Apr 1991). "Homo DNA polymerase alpha gene: sequences decision-making expression in cycling and serum-stimulated cells". Molecular and Cellular Biology. 11 (four): 2081–2095. doi:x.1128/mcb.11.4.2081. PMC359896. PMID 2005899.
Matsumoto T, Eki T, Hurwitz J (Dec 1990). "Studies on the initiation and elongation reactions in the simian virus 40 Dna replication arrangement". Proceedings of the National Academy of Sciences of the The states of America. 87 (24): 9712–9716. Bibcode:1990PNAS...87.9712M. doi:10.1073/pnas.87.24.9712. PMC55243. PMID 2175912.
Hsi KL, Copeland WC, Wang TS (November 1990). "Human DNA polymerase alpha catalytic polypeptide binds ConA and RCA and contains a specific labile site in the N-terminus". Nucleic Acids Research. 18 (21): 6231–6237. doi:10.1093/nar/18.21.6231. PMC332486. PMID 2243771.
Wang TS, Pearson BE, Suomalainen HA, Mohandas T, Shapiro LJ, Schröder J, Korn D (August 1985). "Assignment of the gene for human Deoxyribonucleic acid polymerase alpha to the X chromosome". Proceedings of the National Academy of Sciences of the United States of America. 82 (xvi): 5270–5274. Bibcode:1985PNAS...82.5270W. doi:x.1073/pnas.82.xvi.5270. PMC390549. PMID 2410918.
Knorre DG, Lavrik OI, Nevinsky GA (May 1988). "Poly peptide-nucleic acid interaction in reactions catalyzed with DNA polymerases". Biochimie. 70 (5): 655–661. doi:10.1016/0300-9084(88)90250-7. PMID 3139084.
Nishida C, Reinhard P, Linn S (January 1988). "Dna repair synthesis in human being fibroblasts requires DNA polymerase delta". The Journal of Biological Chemistry. 263 (ane): 501–510. doi:10.1016/S0021-9258(19)57421-X. PMID 3335506.
Wong SW, Wahl AF, Yuan PM, Arai North, Pearson Exist, Arai Yard, et al. (January 1988). "Human DNA polymerase alpha cistron expression is cell proliferation dependent and its master structure is similar to both prokaryotic and eukaryotic replicative Dna polymerases". The EMBO Journal. 7 (1): 37–47. doi:x.1002/j.1460-2075.1988.tb02781.x. PMC454213. PMID 3359994.
Tsuda M, Masuyama M, Katsunuma T (December 1986). "Inhibition of human being DNA polymerase alpha by alpha 1-antichymotrypsin". Cancer Research. 46 (12 Pt 1): 6139–6142. PMID 3490907.
Jackson DA, Cook PR (November 1986). "Different populations of DNA polymerase blastoff in HeLa cells". Journal of Molecular Biology. 192 (1): 77–86. doi:ten.1016/0022-2836(86)90465-1. PMID 3820307.
Miller MR, Seighman C, Ulrich RG (December 1985). "Inhibition of Deoxyribonucleic acid replication and DNA polymerase alpha activity by monoclonal anti-(Dna polymerase alpha) immunoglobulin Yard and F(ab) fragments". Biochemistry. 24 (25): 7440–7445. doi:x.1021/bi00346a061. PMID 4084590.
Bensch KG, Tanaka Southward, Hu SZ, Wang TS, Korn D (July 1982). "Intracellular localization of man DNA polymerase alpha with monoclonal antibodies". The Periodical of Biological Chemistry. 257 (14): 8391–8396. doi:10.1016/S0021-9258(xviii)34344-viii. PMID 7045121.
Tanaka S, Hu SZ, Wang TS, Korn D (July 1982). "Preparation and preliminary characterization of monoclonal antibodies against homo Deoxyribonucleic acid polymerase alpha". The Periodical of Biological Chemical science. 257 (fourteen): 8386–8390. doi:10.1016/S0021-9258(18)34343-6. PMID 7085672.
Eckert KA, Kunkel TA (Nov 1993). "Allegiance of Dna synthesis catalyzed by human Deoxyribonucleic acid polymerase blastoff and HIV-1 contrary transcriptase: effect of reaction pH". Nucleic Acids Research. 21 (22): 5212–5220. doi:x.1093/nar/21.22.5212. PMC310639. PMID 7504813.