POLH (polymerase (DNA direct), eta)

2001-02-01   Anne 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

Identity

HGNC
POLH
LOCATION
6p21.1
LOCUSID
5429
ALIAS
RAD30,RAD30A,XP-V,XPV
FUSION GENES
Show Gene Fusions

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

    • Proteins

    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

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

    Bibliography

    Pubmed IDLast YearTitleAuthors

    Other Information

    Locus ID:

    NCBI: 5429
    MIM: 603968
    HGNC: 9181
    Ensembl: ENSG00000170734

    Variants:

    dbSNP: 5429
    ClinVar: 5429
    TCGA: ENSG00000170734
    COSMIC: POLH

    RNA/Proteins

    Gene IDTranscript IDUniprot
    ENSG00000170734ENST00000372226Q9Y253
    ENSG00000170734ENST00000372236Q9Y253
    ENSG00000170734ENST00000372236A0A024RD62
    ENSG00000170734ENST00000443535Q5JTF2

    Expression (GTEx)

    0
    5
    10
    15
    20
    25
    30
    35
    40
    Adipose - Subcutaneous
    Adipose - Visceral
    Adrenal Gland
    Artery - Aorta
    Artery - Tibial
    Bladder
    Brain - Amygdala
    Brain - Anterior cingulate cortex
    Brain - Caudate
    Brain - Cerebellar Hemisphere
    Brain - Cerebellum
    Brain - Cortex
    Brain - Frontal Cortex
    Brain - Hippocampus
    Brain - Hypothalamus
    Brain - Nucleus accumbens
    Brain - Putamen
    Brain - Spinal cord
    Brain - Substantia nigra
    Breast - Mammary Tissue
    Cells - Cultured fibroblasts
    Cells - EBV - transformed lymphocytes
    Cervix - Ectocervix
    Cervix - Endocervix
    Colon - Sigmoid
    Colon - Transverse
    Esophagus - Gastroesophageal Junction
    Esophagus - Mucosa
    Esophagus - Muscularis
    Fallopian Tube
    Heart - Atrial Appendage
    Heart - Left Ventricle
    Kidney - Cortex
    Kidney - Medulla
    Liver
    Lung
    Minor Salivary Gland
    Muscle - Skeletal
    Nerve - Tibial
    Ovary
    Pancreas
    Pituitary
    Prostate
    Skin - Not Sun Exposed
    Skin - Sun Exposed
    Small Intestine - Terminal Ileum
    Spleen
    Stomach
    Testis
    Thyroid
    Uterus
    Vagina
    Whole Blood

    Pathways

    PathwaySourceExternal ID
    Fanconi anemia pathwayKEGGko03460
    Fanconi anemia pathwayKEGGhsa03460
    DNA RepairREACTOMER-HSA-73894
    DNA Damage BypassREACTOMER-HSA-73893
    Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA templateREACTOMER-HSA-110313
    Translesion Synthesis by POLHREACTOMER-HSA-110320
    Termination of translesion DNA synthesisREACTOMER-HSA-5656169
    DNA Double-Strand Break RepairREACTOMER-HSA-5693532
    Homology Directed RepairREACTOMER-HSA-5693538
    HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA)REACTOMER-HSA-5693567
    HDR through Homologous Recombination (HRR)REACTOMER-HSA-5685942
    Platinum drug resistanceKEGGko01524
    Platinum drug resistanceKEGGhsa01524

    Protein levels (Protein atlas)

    Not detected
    Low
    Medium
    High
    cerebral cortex
    cerebellum
    hippocampus
    caudate
    thyroid gland
    parathyroid gland
    adrenal gland
    nasopharynx
    bronchus
    lung
    oral mucosa
    salivary gland
    esophagus
    stomach 1
    stomach 2
    duodenum
    small intestine
    colon
    rectum
    liver
    gallbladder
    pancreas
    kidney
    urinary bladder
    testis
    epididymis
    seminal vesicle
    prostate
    vagina
    ovary
    fallopian tube
    endometrium 1
    endometrium 2
    cervix, uterine
    placenta
    breast
    heart muscle
    smooth muscle
    skeletal muscle
    soft tissue 1
    soft tissue 2
    adipose tissue
    skin 1
    skin 2
    appendix
    spleen
    lymph node
    tonsil
    bone marrow

    References

    Pubmed IDYearTitleCitations
    151495982004Interaction of human DNA polymerase eta with monoubiquitinated PCNA: a possible mechanism for the polymerase switch in response to DNA damage.344
    163572612005Ubiquitin-binding domains in Y-family polymerases regulate translesion synthesis.304
    205772082010Structure and mechanism of human DNA polymerase eta.159
    149992872004Preferential cis-syn thymine dimer bypass by DNA polymerase eta occurs with biased fidelity.104
    153801062004Co-localization in replication foci and interaction of human Y-family members, DNA polymerase pol eta and REVl protein.89
    167635562006Controlling the subcellular localization of DNA polymerases iota and eta via interactions with ubiquitin.85
    201595582010Regulation of translesion synthesis DNA polymerase eta by monoubiquitination.82
    236095332013DNA synthesis by Pol η promotes fragile site stability by preventing under-replicated DNA in mitosis.79
    244499062014Human Pol ζ purified with accessory subunits is active in translesion DNA synthesis and complements Pol η in cisplatin bypass.73
    198227542009Highly error-free role of DNA polymerase eta in the replicative bypass of UV-induced pyrimidine dimers in mouse and human cells.71

    Citation

    Anne Stary ; Alain Sarasin

    POLH (polymerase (DNA direct), eta)

    Atlas Genet Cytogenet Oncol Haematol. 2001-02-01

    Online version: http://atlasgeneticsoncology.org/gene/303/welcome