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POLH (polymerase (DNA direct), eta)

Written2001-02Anne Stary, Alain Sarasin
Laboratory of Genetic Instability, Cancer, UPR2169 CNRS, Institut de Recherches sur le Cancer, 7, rue guy Moquet, BP 8, 94801 VILLEJUIF, France

(Note : for Links provided by Atlas : click)

Identity

Alias_namespolymerase (DNA directed), eta
polymerase (DNA) eta
Alias_symbol (synonym)RAD30A
XP-V
Other alias
HGNC (Hugo) POLH
LocusID (NCBI) 5429
Atlas_Id 303
Location 6p21.1  [Link to chromosome band 6p21]
Location_base_pair Starts at 43576141 and ends at 43620523 bp from pter ( according to hg19-Feb_2009)  [Mapping POLH.png]
Fusion genes
(updated 2016)		PKP4 (2q24.1) / POLH (6p21.1)POLH (6p21.1) / POLH (6p21.1)cytochrome_b () / POLH (6p21.1)
Note see also the deep insight on: Nucleotide Excision Repair

DNA/RNA

Description 11 exons.
  • Of the 11 splice donor/acceptor sites, 10 contained consensus GT/AG dinucleotides; only the splice donor site in exon 11 (sequence CT) varied from the consensus pattern.
  • The POLH gene lacked a TATA sequence in the region upstream of the transcription-initiation site and the upstream region was GC rich (76% in the sequence between +1 and 270).
  • The first ATG codon for initiation of translation was included in the second exon. Exon 11 contained the termination codon followed by 661 bp of 3'-untranslated sequence

    • Protein

    Description 713 amino acids
    Function The POLH gene encodes DNA polymerase h, which catalyzes the translesion synthesis past a cis-syn T-T pyrimidine dimer, one of the major DNA photoproducts induced by UV light
    Homology mXPV: 80.3% amino acids identity and 86.9% similarity

    Mutations

    Germinal 12 mutated sites involved in the XP variant syndrome

    Implicated in

    Note
      
    Entity xeroderma pigmentosum, XP group V
    Disease predisposition to skin cancer
      

    Bibliography

    Proofreading of DNA polymerase eta-dependent replication errors.
    Bebenek K, Matsuda T, Masutani C, Hanaoka F, Kunkel TA
    The Journal of biological chemistry. 2001 ; 276 (4) : 2317-2320.
    PMID 11113111
     
    Defective postreplication repair in xeroderma pigmentosum variant fibroblasts.
    Boyer JC, Kaufmann WK, Brylawski BP, Cordeiro-Stone M
    Cancer research. 1990 ; 50 (9) : 2593-2598.
    PMID 2109654
     
    Increased ultraviolet sensitivity and chromosomal instability related to P53 function in the xeroderma pigmentosum variant.
    Cleaver JE, Afzal V, Feeney L, McDowell M, Sadinski W, Volpe JP, Busch DB, Coleman DM, Ziffer DW, Yu Y, Nagasawa H, Little JB
    Cancer research. 1999 ; 59 (5) : 1102-1108.
    PMID 10070969
     
    Xeroderma pigmentosum variant and normal fibroblasts show the same response to the inhibition of DNA replication by benzo[a]pyrene-diol-epoxide-I.
    Cordeiro-Stone M, Boyer JC, Smith BA, Kaufmann WK
    Carcinogenesis. 1986 ; 7 (10) : 1783-1786.
    PMID 3093115
     
    Impaired translesion synthesis in xeroderma pigmentosum variant extracts.
    Cordonnier AM, Lehmann AR, Fuchs RP
    Molecular and cellular biology. 1999 ; 19 (3) : 2206-2211.
    PMID 10022907
     
    Defective and enhanced postreplication repair in classical and variant xeroderma pigmentosum cells treated with N-acetoxy-2-acetylaminofluorene.
    D'Ambrosio SM, Setlow RB
    Cancer research. 1978 ; 38 (4) : 1147-1153.
    PMID 639041
     
    Bypass of a site-specific cis-Syn thymine dimer in an SV40 vector during in vitro replication by HeLa and XPV cell-free extracts.
    Ensch-Simon I, Burgers PM, Taylor JS
    Biochemistry. 1998 ; 37 (22) : 8218-8226.
    PMID 9609718
     
    Assignment of six patients with xeroderma pigmentosum in Hokkaido area to a variant form.
    Fujikawa K, Ayaki H, Ishizaki K, Takatera H, Matsuo S, Iizuka H, Koizumi H, Ikenaga M
    Journal of radiation research. 1994 ; 35 (3) : 168-178.
    PMID 7830260
     
    Sloppier copier DNA polymerases involved in genome repair.
    Goodman MF, Tippin B
    Current opinion in genetics & development. 2000 ; 10 (2) : 162-168.
    PMID 10753775
     
    Effect of UV light on DNA chain growth and replicon initiation in xeroderma pigmentosum variant cells.
    Griffiths TD, Ling SY
    Mutagenesis. 1991 ; 6 (4) : 247-251.
    PMID 1943714
     
    Inefficient bypass of an abasic site by DNA polymerase eta.
    Haracska L, Washington MT, Prakash S, Prakash L
    The Journal of biological chemistry. 2001 ; 276 (9) : 6861-6866.
    PMID 11106652
     
    hRAD30 mutations in the variant form of xeroderma pigmentosum.
    Johnson RE, Kondratick CM, Prakash S, Prakash L
    Science (New York, N.Y.). 1999 ; 285 (5425) : 263-265.
    PMID 10398605
     
    Xeroderma pigmentosum variant: generation and characterization of fibroblastic cell lines transformed with SV40 large T antigen.
    King SA, Wilson SJ, Farber RA, Kaufmann WK, Cordeiro-Stone M
    Experimental cell research. 1995 ; 217 (1) : 100-108.
    PMID 7867708
     
    The relationship between pyrimidine dimers and replicating DNA in UV-irradiated human fibroblasts.
    Lehmann AR
    Nucleic acids research. 1979 ; 7 (7) : 1901-1912.
    PMID 231765
     
    Xeroderma pigmentosum cells with normal levels of excision repair have a defect in DNA synthesis after UV-irradiation.
    Lehmann AR, Kirk-Bell S, Arlett CF, Paterson MC, Lohman PH, de Weerd-Kastelein EA, Bootsma D
    Proceedings of the National Academy of Sciences of the United States of America. 1975 ; 72 (1) : 219-223.
    PMID 1054497
     
    Inaugural article: polymerase eta deficiency in the xeroderma pigmentosum variant uncovers an overlap between the S phase checkpoint and double-strand break repair.
    Limoli CL, Giedzinski E, Morgan WF, Cleaver JE
    Proceedings of the National Academy of Sciences of the United States of America. 2000 ; 97 (14) : 7939-7946.
    PMID 10859352
     
    Xeroderma pigmentosum variant (XP-V) correcting protein from HeLa cells has a thymine dimer bypass DNA polymerase activity.
    Masutani C, Araki M, Yamada A, Kusumoto R, Nogimori T, Maekawa T, Iwai S, Hanaoka F
    The EMBO journal. 1999 ; 18 (12) : 3491-3501.
    PMID 10369688
     
    Low fidelity DNA synthesis by human DNA polymerase-eta.
    Matsuda T, Bebenek K, Masutani C, Hanaoka F, Kunkel TA
    Nature. 2000 ; 404 (6781) : 1011-1013.
    PMID 10801132
     
    Abnormal sensitivity of human fibroblasts from xeroderma pigmentosum variants to transformation to anchorage independence by ultraviolet radiation.
    McCormick JJ, Kateley-Kohler S, Watanabe M, Maher VM
    Cancer research. 1986 ; 46 (2) : 489-492.
    PMID 3940626
     
    Abnormal, error-prone bypass of photoproducts by xeroderma pigmentosum variant cell extracts results in extreme strand bias for the kinds of mutations induced by UV light.
    McGregor WG, Wei D, Maher VM, McCormick JJ
    Molecular and cellular biology. 1999 ; 19 (1) : 147-154.
    PMID 9858539
     
    Cytological evidence for DNA chain elongation after UV irradiation in the S phase.
    Minka DF, Nath J
    Biochemical genetics. 1981 ; 19 (3-4) : 199-210.
    PMID 7247930
     
    Defective replication of psoralen adducts detected at the gene-specific level in xeroderma pigmentosum variant cells.
    Misra RR, Vos JM
    Molecular and cellular biology. 1993 ; 13 (2) : 1002-1012.
    PMID 8423773
     
    Induction and repair of (6-4) photoproducts in normal human and xeroderma pigmentosum variant cells during the cell cycle.
    Mitchell DL, Cleaver JE, Lowery MP, Hewitt RR
    Mutation research. 1995 ; 337 (3) : 161-167.
    PMID 7491119
     
    Defective bypass replication of a leading strand cyclobutane thymine dimer in xeroderma pigmentosum variant cell extracts.
    Svoboda DL, Briley LP, Vos JM
    Cancer research. 1998 ; 58 (11) : 2445-2448.
    PMID 9622087
     
    Comparison of the rate of excision of major UV photoproducts in the strands of the human HPRT gene of normal and xeroderma pigmentosum variant cells.
    Tung BS, McGregor WG, Wang YC, Maher VM, McCormick JJ
    Mutation research. 1996 ; 362 (1) : 65-74.
    PMID 8538650
     
    Xeroderma pigmentosum variant cells are less likely than normal cells to incorporate dAMP opposite photoproducts during replication of UV-irradiated plasmids.
    Wang YC, Maher VM, McCormick JJ
    Proceedings of the National Academy of Sciences of the United States of America. 1991 ; 88 (17) : 7810-7814.
    PMID 1652764
     
    Ultraviolet hypermutability of a shuttle vector propagated in xeroderma pigmentosum variant cells.
    Waters HL, Seetharam S, Seidman MM, Kraemer KH
    The Journal of investigative dermatology. 1993 ; 101 (5) : 744-748.
    PMID 8228338
     
    Complementation of defective translesion synthesis and UV light sensitivity in xeroderma pigmentosum variant cells by human and mouse DNA polymerase eta.
    Yamada A, Masutani C, Iwai S, Hanaoka F
    Nucleic acids research. 2000 ; 28 (13) : 2473-2480.
    PMID 10871396
     
    Genomic structure, chromosomal localization and identification of mutations in the xeroderma pigmentosum variant (XPV) gene.
    Yuasa M, Masutani C, Eki T, Hanaoka F
    Oncogene. 2000 ; 19 (41) : 4721-4728.
    PMID 11032022
     
    Error-prone lesion bypass by human DNA polymerase eta.
    Zhang Y, Yuan F, Wu X, Rechkoblit O, Taylor JS, Geacintov NE, Wang Z
    Nucleic acids research. 2000 ; 28 (23) : 4717-4724.
    PMID 11095682
     

    Citation

    This paper should be referenced as such :
    Stary, A ; Sarasin, A
    POLH (polymerase (DNA direct), eta)
    Atlas Genet Cytogenet Oncol Haematol. 2001;5(2):98-99.
    Free journal version : [ pdf ]   [ DOI ]
    On line version : http://AtlasGeneticsOncology.org/Genes/XPVID303.html

    Other Cancer prone implicated (Data extracted from papers in the Atlas) [ 1 ]
      Xeroderma pigmentosum

    External links

    Nomenclature
    HGNC (Hugo)POLH   9181
    LRG (Locus Reference Genomic)LRG_470
    Cards
    AtlasXPVID303
    Entrez_Gene (NCBI)POLH  5429  DNA polymerase eta
    AliasesRAD30; RAD30A; XP-V; XPV
    GeneCards (Weizmann)POLH
    Ensembl hg19 (Hinxton)ENSG00000170734 [Gene_View]
    Ensembl hg38 (Hinxton)ENSG00000170734 [Gene_View]  chr6:43576141-43620523 [Contig_View]  POLH [Vega]
    ICGC DataPortalENSG00000170734
    TCGA cBioPortalPOLH
    AceView (NCBI)POLH
    Genatlas (Paris)POLH
    WikiGenes5429
    SOURCE (Princeton)POLH
    Genetics Home Reference (NIH)POLH
    Genomic and cartography
    GoldenPath hg38 (UCSC)POLH  -     chr6:43576141-43620523 +  6p21.1   [Description]    (hg38-Dec_2013)
    GoldenPath hg19 (UCSC)POLH  -     6p21.1   [Description]    (hg19-Feb_2009)
    EnsemblPOLH - 6p21.1 [CytoView hg19]  POLH - 6p21.1 [CytoView hg38]
    Mapping of homologs : NCBIPOLH [Mapview hg19]  POLH [Mapview hg38]
    OMIM278750   603968   
    Gene and transcription
    Genbank (Entrez)AB024313 AF158185 AF241258 AJ420484 AK023893
    RefSeq transcript (Entrez)NM_001291969 NM_001291970 NM_006502
    RefSeq genomic (Entrez)
    Consensus coding sequences : CCDS (NCBI)POLH
    Cluster EST : UnigeneHs.655467 [ NCBI ]
    CGAP (NCI)Hs.655467
    Alternative Splicing GalleryENSG00000170734
    Gene ExpressionPOLH [ NCBI-GEO ]   POLH [ EBI - ARRAY_EXPRESS ]   POLH [ SEEK ]   POLH [ MEM ]
    Gene Expression Viewer (FireBrowse)POLH [ Firebrowse - Broad ]
    SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
    GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
    BioGPS (Tissue expression)5429
    GTEX Portal (Tissue expression)POLH
    Protein : pattern, domain, 3D structure
    UniProt/SwissProtQ9Y253   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
    NextProtQ9Y253  [Sequence]  [Exons]  [Medical]  [Publications]
    With graphics : InterProQ9Y253
    Splice isoforms : SwissVarQ9Y253
    Catalytic activity : Enzyme2.7.7.7 [ Enzyme-Expasy ]   2.7.7.72.7.7.7 [ IntEnz-EBI ]   2.7.7.7 [ BRENDA ]   2.7.7.7 [ KEGG ]   
    PhosPhoSitePlusQ9Y253
    Domaine pattern : Prosite (Expaxy)UMUC (PS50173)   
    Domains : Interpro (EBI)DNA_pol_eta/kappa    DNA_pol_Y-fam_little_finger    UmuC   
    Domain families : Pfam (Sanger)IMS (PF00817)    IMS_C (PF11799)   
    Domain families : Pfam (NCBI)pfam00817    pfam11799   
    Conserved Domain (NCBI)POLH
    DMDM Disease mutations5429
    Blocks (Seattle)POLH
    PDB (SRS)###############################################################################################################################################################################################################################################################   
    PDB (PDBSum)###############################################################################################################################################################################################################################################################   
    PDB (IMB)###############################################################################################################################################################################################################################################################   
    PDB (RSDB)###############################################################################################################################################################################################################################################################   
    Structural Biology KnowledgeBase###############################################################################################################################################################################################################################################################   
    SCOP (Structural Classification of Proteins)###############################################################################################################################################################################################################################################################   
    CATH (Classification of proteins structures)###############################################################################################################################################################################################################################################################   
    SuperfamilyQ9Y253
    Human Protein AtlasENSG00000170734
    Peptide AtlasQ9Y253
    HPRD04913
    IPIIPI00008011   IPI00552037   IPI00646080   
    Protein Interaction databases
    DIP (DOE-UCLA)Q9Y253
    IntAct (EBI)Q9Y253
    FunCoupENSG00000170734
    BioGRIDPOLH
    STRING (EMBL)POLH
    ZODIACPOLH
    Ontologies - Pathways
    QuickGOQ9Y253
    Ontology : AmiGODNA synthesis involved in DNA repair  damaged DNA binding  DNA-directed DNA polymerase activity  protein binding  nucleoplasm  nucleoplasm  cytosol  DNA replication  DNA repair  regulation of DNA repair  pyrimidine dimer repair  response to UV-C  translesion synthesis  metal ion binding  error-free translesion synthesis  cellular response to UV-C  
    Ontology : EGO-EBIDNA synthesis involved in DNA repair  damaged DNA binding  DNA-directed DNA polymerase activity  protein binding  nucleoplasm  nucleoplasm  cytosol  DNA replication  DNA repair  regulation of DNA repair  pyrimidine dimer repair  response to UV-C  translesion synthesis  metal ion binding  error-free translesion synthesis  cellular response to UV-C  
    Pathways : KEGGFanconi anemia pathway   
    REACTOMEQ9Y253 [protein]
    REACTOME PathwaysR-HSA-5685942 [pathway]   
    NDEx NetworkPOLH
    Atlas of Cancer Signalling NetworkPOLH
    Wikipedia pathwaysPOLH
    Orthology - Evolution
    OrthoDB5429
    GeneTree (enSembl)ENSG00000170734
    Phylogenetic Trees/Animal Genes : TreeFamPOLH
    HOVERGENQ9Y253
    HOGENOMQ9Y253
    Homologs : HomoloGenePOLH
    Homology/Alignments : Family Browser (UCSC)POLH
    Gene fusions - Rearrangements
    Fusion Cancer (Beijing)cytochrome_b [POLH]  -  6p21.1 [FUSC000524]
    Polymorphisms : SNP and Copy number variants
    NCBI Variation ViewerPOLH [hg38]
    dbSNP Single Nucleotide Polymorphism (NCBI)POLH
    dbVarPOLH
    ClinVarPOLH
    1000_GenomesPOLH 
    Exome Variant ServerPOLH
    ExAC (Exome Aggregation Consortium)POLH (select the gene name)
    Genetic variants : HAPMAP5429
    Genomic Variants (DGV)POLH [DGVbeta]
    DECIPHERPOLH [patients]   [syndromes]   [variants]   [genes]  
    CONAN: Copy Number AnalysisPOLH 
    Mutations
    ICGC Data PortalPOLH 
    TCGA Data PortalPOLH 
    Broad Tumor PortalPOLH
    OASIS PortalPOLH [ Somatic mutations - Copy number]
    Somatic Mutations in Cancer : COSMICPOLH  [overview]  [genome browser]  [tissue]  [distribution]  
    Mutations and Diseases : HGMDPOLH
    LOVD (Leiden Open Variation Database)Whole genome datasets
    LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
    BioMutasearch POLH
    DgiDB (Drug Gene Interaction Database)POLH
    DoCM (Curated mutations)POLH (select the gene name)
    CIViC (Clinical Interpretations of Variants in Cancer)POLH (select a term)
    intoGenPOLH
    NCG5 (London)POLH
    Cancer3DPOLH(select the gene name)
    Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
    Diseases
    OMIM278750    603968   
    Orphanet12020   
    MedgenPOLH
    Genetic Testing Registry POLH
    NextProtQ9Y253 [Medical]
    TSGene5429
    GENETestsPOLH
    Target ValidationPOLH
    Huge Navigator POLH [HugePedia]
    snp3D : Map Gene to Disease5429
    BioCentury BCIQPOLH
    ClinGenPOLH
    Clinical trials, drugs, therapy
    Chemical/Protein Interactions : CTD5429
    Chemical/Pharm GKB GenePA279
    Clinical trialPOLH
    Miscellaneous
    canSAR (ICR)POLH (select the gene name)
    Probes
    Litterature
    PubMed148 Pubmed reference(s) in Entrez
    GeneRIFsGene References Into Functions (Entrez)
    CoreMinePOLH
    EVEXPOLH
    GoPubMedPOLH
    iHOPPOLH
    REVIEW articlesautomatic search in PubMed
    Last year publicationsautomatic search in PubMed

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    indexed on : Fri Jun 30 11:21:44 CEST 2017
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