LOCUS       NM_002691               3436 bp    mRNA    linear   PRI 04-AUG-2024
DEFINITION  Homo sapiens DNA polymerase delta 1, catalytic subunit (POLD1),
            transcript variant 2, mRNA.
ACCESSION   NM_002691
VERSION     NM_002691.4
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 3436)
  AUTHORS   Andrianova,M.A., Seplyarskiy,V.B., Terradas,M., Sanchez-Heras,A.B.,
            Mur,P., Soto,J.L., Aiza,G., Borras,E., Kondrashov,F.A.,
            Kondrashov,A.S., Bazykin,G.A. and Valle,L.
  TITLE     Discovery of recessive effect of human polymerase delta
            proofreading deficiency through mutational analysis of
            POLD1-mutated normal and cancer cells
  JOURNAL   Eur J Hum Genet 32 (7), 837-845 (2024)
   PUBMED   38658779
  REMARK    GeneRIF: Discovery of recessive effect of human polymerase delta
            proofreading deficiency through mutational analysis of
            POLD1-mutated normal and cancer cells.
REFERENCE   2  (bases 1 to 3436)
  AUTHORS   Shimizu,D., Ishibashi,M., Yamada,T., Toda,Y., Hosogi,S. and
            Ashihara,E.
  TITLE     POLD1 Is Required for Cell Cycle Progression by Overcoming DNA
            Damage in Malignant Pleural Mesothelioma
  JOURNAL   Cancer Genomics Proteomics 21 (2), 158-165 (2024)
   PUBMED   38423601
  REMARK    GeneRIF: POLD1 Is Required for Cell Cycle Progression by Overcoming
            DNA Damage in Malignant Pleural Mesothelioma.
REFERENCE   3  (bases 1 to 3436)
  AUTHORS   Zheng,S., Donnelly,E.D. and Strauss,J.B.
  TITLE     Race, Prevalence of POLE and POLD1 Alterations, and Survival Among
            Patients With Endometrial Cancer
  JOURNAL   JAMA Netw Open 7 (1), e2351906 (2024)
   PUBMED   38231514
  REMARK    GeneRIF: Race, Prevalence of POLE and POLD1 Alterations, and
            Survival Among Patients With Endometrial Cancer.
            Publication Status: Online-Only
REFERENCE   4  (bases 1 to 3436)
  AUTHORS   Zhao,L. and Chang,L.S.
  TITLE     The human POLD1 gene. Identification of an upstream activator
            sequence, activation by Sp1 and Sp3, and cell cycle regulation
  JOURNAL   J Biol Chem 272 (8), 4869-4882 (1997)
   PUBMED   9030545
REFERENCE   5  (bases 1 to 3436)
  AUTHORS   Chang,L.S., Zhao,L., Zhu,L., Chen,M.L. and Lee,M.Y.
  TITLE     Structure of the gene for the catalytic subunit of human DNA
            polymerase delta (POLD1)
  JOURNAL   Genomics 28 (3), 411-419 (1995)
   PUBMED   7490075
REFERENCE   6  (bases 1 to 3436)
  AUTHORS   Kemper,R.R., Ahn,E.R., Zhang,P., Lee,M.Y. and Rabin,M.
  TITLE     Human DNA polymerase delta gene maps to region 19q13.3-q13.4 by in
            situ hybridization
  JOURNAL   Genomics 14 (1), 205-206 (1992)
   PUBMED   1427831
REFERENCE   7  (bases 1 to 3436)
  AUTHORS   Yang,C.L., Chang,L.S., Zhang,P., Hao,H., Zhu,L., Toomey,N.L. and
            Lee,M.Y.
  TITLE     Molecular cloning of the cDNA for the catalytic subunit of human
            DNA polymerase delta
  JOURNAL   Nucleic Acids Res 20 (4), 735-745 (1992)
   PUBMED   1542570
REFERENCE   8  (bases 1 to 3436)
  AUTHORS   Popanda,O. and Thielmann,H.W.
  TITLE     The function of DNA polymerases in DNA repair synthesis of
            ultraviolet-irradiated human fibroblasts
  JOURNAL   Biochim Biophys Acta 1129 (2), 155-160 (1992)
   PUBMED   1730053
REFERENCE   9  (bases 1 to 3436)
  AUTHORS   Chung,D.W., Zhang,J.A., Tan,C.K., Davie,E.W., So,A.G. and
            Downey,K.M.
  TITLE     Primary structure of the catalytic subunit of human DNA polymerase
            delta and chromosomal location of the gene
  JOURNAL   Proc Natl Acad Sci U S A 88 (24), 11197-11201 (1991)
   PUBMED   1722322
REFERENCE   10 (bases 1 to 3436)
  AUTHORS   Lee,M.Y. and Toomey,N.L.
  TITLE     Human placental DNA polymerase delta: identification of a
            170-kilodalton polypeptide by activity staining and immunoblotting
  JOURNAL   Biochemistry 26 (4), 1076-1085 (1987)
   PUBMED   2436659
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from CD101690.1, M81735.1 and
            AB209560.1.
            
            On Jun 2, 2019 this sequence version replaced NM_002691.3.
            
            Summary: This gene encodes the 125-kDa catalytic subunit of DNA
            polymerase delta. DNA polymerase delta possesses both polymerase
            and 3' to 5' exonuclease activity and plays a critical role in DNA
            replication and repair. Alternatively spliced transcript variants
            have been observed for this gene, and a pseudogene of this gene is
            located on the long arm of chromosome 6. [provided by RefSeq, Mar
            2012].
            
            Transcript Variant: This variant (2) contains an alternate exon in
            the 5' UTR and uses an alternate splice site in the 3' coding
            region, compared to variant 4. The encoded isoform (1) is shorter
            than isoform 2.
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: M81735.1, SRR1803613.286619.1
                                           [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000440232.7/ ENSP00000406046.1
            RefSeq Select criteria :: based on manual assertion, conservation,
                                      expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-3                 CD101690.1         51-53
            4-400               M81735.1           1-397
            401-2538            AB209560.1         544-2681
            2539-3436           M81735.1           2536-3433
FEATURES             Location/Qualifiers
     source          1..3436
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="19"
                     /map="19q13.33"
     gene            1..3436
                     /gene="POLD1"
                     /gene_synonym="CDC2; CRCS10; IMD120; MDPL; POLD"
                     /note="DNA polymerase delta 1, catalytic subunit"
                     /db_xref="GeneID:5424"
                     /db_xref="HGNC:HGNC:9175"
                     /db_xref="MIM:174761"
     exon            1..44
                     /gene="POLD1"
                     /gene_synonym="CDC2; CRCS10; IMD120; MDPL; POLD"
                     /inference="alignment:Splign:2.1.0"
     exon            45..247
                     /gene="POLD1"
                     /gene_synonym="CDC2; CRCS10; IMD120; MDPL; POLD"
                     /inference="alignment:Splign:2.1.0"
     CDS             46..3369
                     /gene="POLD1"
                     /gene_synonym="CDC2; CRCS10; IMD120; MDPL; POLD"
                     /EC_number="2.7.7.7"
                     /note="isoform 1 is encoded by transcript variant 2; CDC2
                     homolog; DNA polymerase subunit delta p125; 3'-5'
                     exodeoxyribonuclease; polymerase (DNA directed), delta 1,
                     catalytic subunit 125kDa; polymerase (DNA) delta 1,
                     catalytic subunit"
                     /codon_start=1
                     /product="DNA polymerase delta catalytic subunit isoform
                     1"
                     /protein_id="NP_002682.2"
                     /db_xref="CCDS:CCDS12795.1"
                     /db_xref="GeneID:5424"
                     /db_xref="HGNC:HGNC:9175"
                     /db_xref="MIM:174761"
                     /translation="MDGKRRPGPGPGVPPKRARGGLWDDDDAPRPSQFEEDLALMEEM
                     EAEHRLQEQEEEELQSVLEGVADGQVPPSAIDPRWLRPTPPALDPQTEPLIFQQLEID
                     HYVGPAQPVPGGPPPSRGSVPVLRAFGVTDEGFSVCCHIHGFAPYFYTPAPPGFGPEH
                     MGDLQRELNLAISRDSRGGRELTGPAVLAVELCSRESMFGYHGHGPSPFLRITVALPR
                     LVAPARRLLEQGIRVAGLGTPSFAPYEANVDFEIRFMVDTDIVGCNWLELPAGKYALR
                     LKEKATQCQLEADVLWSDVVSHPPEGPWQRIAPLRVLSFDIECAGRKGIFPEPERDPV
                     IQICSLGLRWGEPEPFLRLALTLRPCAPILGAKVQSYEKEEDLLQAWSTFIRIMDPDV
                     ITGYNIQNFDLPYLISRAQTLKVQTFPFLGRVAGLCSNIRDSSFQSKQTGRRDTKVVS
                     MVGRVQMDMLQVLLREYKLRSYTLNAVSFHFLGEQKEDVQHSIITDLQNGNDQTRRRL
                     AVYCLKDAYLPLRLLERLMVLVNAVEMARVTGVPLSYLLSRGQQVKVVSQLLRQAMHE
                     GLLMPVVKSEGGEDYTGATVIEPLKGYYDVPIATLDFSSLYPSIMMAHNLCYTTLLRP
                     GTAQKLGLTEDQFIRTPTGDEFVKTSVRKGLLPQILENLLSARKRAKAELAKETDPLR
                     RQVLDGRQLALKVSANSVYGFTGAQVGKLPCLEISQSVTGFGRQMIEKTKQLVESKYT
                     VENGYSTSAKVVYGDTDSVMCRFGVSSVAEAMALGREAADWVSGHFPSPIRLEFEKVY
                     FPYLLISKKRYAGLLFSSRPDAHDRMDCKGLEAVRRDNCPLVANLVTASLRRLLIDRD
                     PEGAVAHAQDVISDLLCNRIDISQLVITKELTRAASDYAGKQAHVELAERMRKRDPGS
                     APSLGDRVPYVIISAAKGVAAYMKSEDPLFVLEHSLPIDTQYYLEQQLAKPLLRIFEP
                     ILGEGRAEAVLLRGDHTRCKTVLTGKVGGLLAFAKRRNCCIGCRTVLSHQGAVCEFCQ
                     PRESELYQKEVSHLNALEERFSRLWTQCQRCQGSLHEDVICTSRDCPIFYMRKKVRKD
                     LEDQEQLLRRFGPPGPEAW"
     exon            248..361
                     /gene="POLD1"
                     /gene_synonym="CDC2; CRCS10; IMD120; MDPL; POLD"
                     /inference="alignment:Splign:2.1.0"
     exon            362..508
                     /gene="POLD1"
                     /gene_synonym="CDC2; CRCS10; IMD120; MDPL; POLD"
                     /inference="alignment:Splign:2.1.0"
     exon            509..634
                     /gene="POLD1"
                     /gene_synonym="CDC2; CRCS10; IMD120; MDPL; POLD"
                     /inference="alignment:Splign:2.1.0"
     exon            635..803
                     /gene="POLD1"
                     /gene_synonym="CDC2; CRCS10; IMD120; MDPL; POLD"
                     /inference="alignment:Splign:2.1.0"
     exon            804..885
                     /gene="POLD1"
                     /gene_synonym="CDC2; CRCS10; IMD120; MDPL; POLD"
                     /inference="alignment:Splign:2.1.0"
     exon            886..1015
                     /gene="POLD1"
                     /gene_synonym="CDC2; CRCS10; IMD120; MDPL; POLD"
                     /inference="alignment:Splign:2.1.0"
     exon            1016..1182
                     /gene="POLD1"
                     /gene_synonym="CDC2; CRCS10; IMD120; MDPL; POLD"
                     /inference="alignment:Splign:2.1.0"
     exon            1183..1287
                     /gene="POLD1"
                     /gene_synonym="CDC2; CRCS10; IMD120; MDPL; POLD"
                     /inference="alignment:Splign:2.1.0"
     exon            1288..1428
                     /gene="POLD1"
                     /gene_synonym="CDC2; CRCS10; IMD120; MDPL; POLD"
                     /inference="alignment:Splign:2.1.0"
     exon            1429..1539
                     /gene="POLD1"
                     /gene_synonym="CDC2; CRCS10; IMD120; MDPL; POLD"
                     /inference="alignment:Splign:2.1.0"
     exon            1540..1731
                     /gene="POLD1"
                     /gene_synonym="CDC2; CRCS10; IMD120; MDPL; POLD"
                     /inference="alignment:Splign:2.1.0"
     exon            1732..1820
                     /gene="POLD1"
                     /gene_synonym="CDC2; CRCS10; IMD120; MDPL; POLD"
                     /inference="alignment:Splign:2.1.0"
     exon            1821..1937
                     /gene="POLD1"
                     /gene_synonym="CDC2; CRCS10; IMD120; MDPL; POLD"
                     /inference="alignment:Splign:2.1.0"
     exon            1938..2051
                     /gene="POLD1"
                     /gene_synonym="CDC2; CRCS10; IMD120; MDPL; POLD"
                     /inference="alignment:Splign:2.1.0"
     exon            2052..2199
                     /gene="POLD1"
                     /gene_synonym="CDC2; CRCS10; IMD120; MDPL; POLD"
                     /inference="alignment:Splign:2.1.0"
     exon            2200..2295
                     /gene="POLD1"
                     /gene_synonym="CDC2; CRCS10; IMD120; MDPL; POLD"
                     /inference="alignment:Splign:2.1.0"
     exon            2296..2433
                     /gene="POLD1"
                     /gene_synonym="CDC2; CRCS10; IMD120; MDPL; POLD"
                     /inference="alignment:Splign:2.1.0"
     exon            2434..2609
                     /gene="POLD1"
                     /gene_synonym="CDC2; CRCS10; IMD120; MDPL; POLD"
                     /inference="alignment:Splign:2.1.0"
     exon            2610..2762
                     /gene="POLD1"
                     /gene_synonym="CDC2; CRCS10; IMD120; MDPL; POLD"
                     /inference="alignment:Splign:2.1.0"
     exon            2763..2865
                     /gene="POLD1"
                     /gene_synonym="CDC2; CRCS10; IMD120; MDPL; POLD"
                     /inference="alignment:Splign:2.1.0"
     exon            2866..2998
                     /gene="POLD1"
                     /gene_synonym="CDC2; CRCS10; IMD120; MDPL; POLD"
                     /inference="alignment:Splign:2.1.0"
     exon            2999..3112
                     /gene="POLD1"
                     /gene_synonym="CDC2; CRCS10; IMD120; MDPL; POLD"
                     /inference="alignment:Splign:2.1.0"
     exon            3113..3165
                     /gene="POLD1"
                     /gene_synonym="CDC2; CRCS10; IMD120; MDPL; POLD"
                     /inference="alignment:Splign:2.1.0"
     exon            3166..3263
                     /gene="POLD1"
                     /gene_synonym="CDC2; CRCS10; IMD120; MDPL; POLD"
                     /inference="alignment:Splign:2.1.0"
     exon            3264..3436
                     /gene="POLD1"
                     /gene_synonym="CDC2; CRCS10; IMD120; MDPL; POLD"
                     /inference="alignment:Splign:2.1.0"
     regulatory      3414..3419
                     /regulatory_class="polyA_signal_sequence"
                     /gene="POLD1"
                     /gene_synonym="CDC2; CRCS10; IMD120; MDPL; POLD"
                     /note="hexamer: AATAAA"
     polyA_site      3436
                     /gene="POLD1"
                     /gene_synonym="CDC2; CRCS10; IMD120; MDPL; POLD"
                     /note="major polyA site"
ORIGIN      
        1 gtcacggcgg cgtaggctgt ggcgggaaac gctgtttgaa gcgggatgga tggcaagcgg
       61 cggccaggcc cagggcccgg ggtgccccca aagcgggccc gtgggggcct ctgggatgat
      121 gatgatgcac ctcggccatc ccaattcgag gaggacctgg cactgatgga ggagatggag
      181 gcagaacaca ggctgcagga gcaggaggag gaggagctgc agtcagtcct ggagggggtt
      241 gcagacgggc aggtcccacc atcagccata gatcctcgct ggcttcggcc cacaccacca
      301 gcgctggacc cccagacaga gcccctcatc ttccaacagt tggagattga ccattatgtg
      361 ggcccagcgc agcctgtgcc tggggggccc ccaccatccc gcggctccgt gcctgtgctc
      421 cgcgccttcg gggtcaccga tgaggggttc tctgtctgct gccacatcca cggcttcgct
      481 ccctacttct acaccccagc gccccctggt ttcgggcccg agcacatggg tgacctgcaa
      541 cgggagctga acttggccat cagccgggac agtcgcgggg ggagggagct gactgggccg
      601 gccgtgctgg ctgtggaact gtgctcccga gagagcatgt ttgggtacca cgggcacggc
      661 ccctccccgt tcctgcgcat caccgtggcg ctgccgcgcc tcgtggcccc ggcccgccgt
      721 ctcctggaac agggcatccg tgtggcaggc ctgggcacgc ccagcttcgc gccctacgag
      781 gccaacgtcg actttgagat ccggttcatg gtggacacgg acatcgtcgg ctgcaactgg
      841 ctggagctcc cagctgggaa atacgccctg aggctgaagg agaaggctac gcagtgccag
      901 ctggaggcgg acgtgctgtg gtctgacgtg gtcagtcacc caccggaagg gccatggcag
      961 cgcattgcgc ccttgcgcgt gctcagcttc gatatcgagt gcgccggccg caaaggcatc
     1021 ttccctgagc ctgagcggga ccctgtcatc cagatctgct cgctgggcct gcgctggggg
     1081 gagccggagc ccttcctacg cctggcgctc accctgcggc cctgtgcccc catcctgggt
     1141 gccaaggtgc agagctacga gaaggaggag gacctgctgc aggcctggtc caccttcatc
     1201 cgtatcatgg accccgacgt gatcaccggt tacaacatcc agaacttcga ccttccgtac
     1261 ctcatctctc gggcccagac cctcaaggta caaacattcc ctttcctggg ccgtgtggcc
     1321 ggcctttgct ccaacatccg ggactcttca ttccagtcca agcagacggg ccggcgggac
     1381 accaaggttg tcagcatggt gggccgcgtg cagatggaca tgctgcaggt gctgctgcgg
     1441 gagtacaagc tccgctccta cacgctcaat gccgtgagct tccacttcct gggcgagcag
     1501 aaggaggacg tgcagcacag catcatcacc gacctgcaga atgggaacga ccagacccgc
     1561 cgccgcctgg ctgtgtactg cctgaaggat gcctacctgc cactgcggct gctggagcgg
     1621 ctcatggtgc tggtgaacgc cgtggagatg gcgagggtca ctggcgtgcc cctcagctac
     1681 ctgctcagtc gtggccagca ggtcaaggtc gtatcccagc tgttgcggca ggccatgcac
     1741 gaggggctgc tgatgcccgt ggtgaagtca gagggcggcg aggactacac gggagccact
     1801 gtcatcgagc ccctcaaagg gtactacgac gtccccatcg ccaccctgga cttctcctcg
     1861 ctgtacccgt ccatcatgat ggcccacaac ctgtgttaca ccacgctcct tcggcccggg
     1921 actgcacaga aactgggcct gactgaggat cagttcatca ggacccccac cggggacgag
     1981 tttgtgaaga cctcagtgcg gaaggggctg ctgccccaga tcctggagaa cctgctcagt
     2041 gcccggaaga gggccaaggc cgagctggcc aaggagacag accccctccg gcgccaggtc
     2101 ctggatggac ggcagctggc gctgaaggtg agcgccaact ccgtatacgg cttcactggc
     2161 gcccaggtgg gcaagttgcc gtgcctggag atctcacaga gcgtcacggg gttcggacgt
     2221 cagatgatcg agaaaaccaa gcagctggtg gagtctaagt acacagtgga gaatggctac
     2281 agcaccagtg ccaaggtggt gtatggtgac actgactccg tcatgtgccg attcggcgtg
     2341 tcctcggtgg ctgaggcgat ggccctgggg cgggaggccg cggactgggt gtcaggtcac
     2401 ttcccgtcgc ccatccggct ggagtttgag aaggtctact tcccatacct gcttatcagc
     2461 aagaagcgct acgcgggcct gctcttctcc tcccggcccg acgcccacga ccgcatggac
     2521 tgcaagggcc tggaggccgt gcgcagggac aactgccccc tcgtggccaa cctggtcact
     2581 gcctcactgc gccgcctgct catcgaccga gaccctgagg gcgcggtggc tcacgcacag
     2641 gacgtcatct cggacctgct gtgcaaccgc atcgatatct cccagctggt catcaccaag
     2701 gagctgaccc gcgcggcctc cgactatgcc ggcaagcagg cccacgtgga gctggccgag
     2761 aggatgagga agcgggaccc cgggagtgcg cccagcctgg gcgaccgcgt cccctacgtg
     2821 atcatcagtg ccgccaaggg tgtggccgcc tacatgaagt cggaggaccc gctgttcgtg
     2881 ctggagcaca gcctgcccat tgacacgcag tactacctgg agcagcagct ggccaagccc
     2941 ctcctgcgca tcttcgagcc catcctgggc gagggccgtg ccgaggctgt gctactgcgg
     3001 ggggaccaca cgcgctgcaa gacggtgctc acgggcaagg tgggcggcct cctggccttc
     3061 gccaaacgcc gcaactgctg cattggctgc cgcacagtgc tcagccacca gggagccgtg
     3121 tgtgagttct gccagccccg ggagtctgag ctgtatcaga aggaggtatc ccatctgaat
     3181 gccctggagg agcgcttctc gcgcctctgg acgcagtgcc agcgctgcca gggcagcctg
     3241 cacgaggacg tcatctgcac cagccgggac tgccccatct tctacatgcg caagaaggtg
     3301 cggaaggacc tggaagacca ggagcagctc ctgcggcgct tcggaccccc tggacctgag
     3361 gcctggtgac cttgcaagca tcccatgggg cgggggcggg accagggaga attaataaag
     3421 ttctggactt ttgcta
//
