DNA polymerase eta

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Polymerase (DNA directed), eta
Protein POLH PDB 2i5o.png
PDB rendering based on 2i5o, the solution structure of the Ubiquitin-Binding Zinc Finger (UBZ) Domain of the Human DNA Y-Polymerase Eta.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols POLH ; RAD30; RAD30A; XP-V; XPV
External IDs OMIM603968 MGI1891457 HomoloGene38189 ChEMBL: 5542 GeneCards: POLH Gene
EC number 2.7.7.7
RNA expression pattern
PBB GE POLH 219380 x at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 5429 80905
Ensembl ENSG00000170734 ENSMUSG00000023953
UniProt Q9Y253 Q9JJN0
RefSeq (mRNA) NM_001291969 NM_030715
RefSeq (protein) NP_001278898 NP_109640
Location (UCSC) Chr 6:
43.54 – 43.59 Mb
Chr 17:
46.17 – 46.2 Mb
PubMed search [1] [2]

DNA polymerase eta (Pol η), is a protein that in humans is encoded by the POLH gene.[1][2][3]

DNA polymerase eta is a eukaryotic DNA polymerase involved in the DNA repair by translesion synthesis. The gene encoding DNA polymerase eta is POLH, also known as XPV, because loss of this gene results in the disease xeroderma pigmentosum. Polymerase eta is particularly important for allowing accurate translesion synthesis of DNA damage resulting from ultraviolet radiation or UV.

Function[edit]

This gene encodes a member of the Y family of specialized DNA polymerases. It copies undamaged DNA with a lower fidelity than other DNA-directed polymerases. However, it accurately replicates UV-damaged DNA; when thymine dimers are present, this polymerase inserts the complementary nucleotides in the newly synthesized DNA, thereby bypassing the lesion and suppressing the mutagenic effect of UV-induced DNA damage. This polymerase is thought to be involved in hypermutation during immunoglobulin class switch recombination.[1] Mutations in this gene result in XPV, a variant type of xeroderma pigmentosum.[4]

Clinical significance[edit]

Xeroderma pigmentosum (XP) is an autosomal recessive human disease characterized by sunlight sensitivity, cutaneous and ocular deterioration, and premature malignant skin neoplasms after exposure to sunlight. XP has been classified into eight complementation groups, XP-A to XP-G and XP-V. Cells from XP-A to XP-G patients have defects in the process of nucleotide excision repair (NER), which eliminates a wide variety of structurally unrelated lesions, including ultraviolet light (UV)-induced cyclobutane pyrimidine dimers (CPD) and (6-4) photoproducts, as well as certain chemical adducts. The genes and proteins of XP groups A, B, C, D, F and G have been isolated and found to represent some of the subunits of the core NER machinery. In contrast, cells belonging to the eighth group, XP variant (XP-V), are NER-proficient but display abnormal DNA replication, including reduced ability to elongate nascent DNA strands on UV-irradiated DNA. Thus, the XP-V gene product is likely to be involved in the process of DNA replication on damaged DNA known as post-replication repair, but not in NER

Interactions[edit]

POLH has been shown to interact with PCNA.[5]

References[edit]

  1. ^ a b "Entrez Gene: POLH polymerase (DNA directed), eta". 
  2. ^ Masutani C, Kusumoto R, Yamada A, Dohmae N, Yokoi M, Yuasa M, Araki M, Iwai S, Takio K, Hanaoka F (June 1999). "The XPV (xeroderma pigmentosum variant) gene encodes human DNA polymerase eta". Nature 399 (6737): 700–4. doi:10.1038/21447. PMID 10385124. 
  3. ^ Johnson RE, Kondratick CM, Prakash S, Prakash L (July 1999). "hRAD30 mutations in the variant form of xeroderma pigmentosum". Science 285 (5425): 263–5. doi:10.1126/science.285.5425.263. PMID 10398605. 
  4. ^ Stary A, Sarasin A (September 2002). "Molecular mechanisms of UV-induced mutations as revealed by the study of DNA polymerase eta in human cells". Res. Microbiol. 153 (7): 441–5. doi:10.1016/S0923-2508(02)01343-8. PMID 12405351. 
  5. ^ Haracska L, Johnson RE, Unk I, Phillips B, Hurwitz J, Prakash L, Prakash S (November 2001). "Physical and functional interactions of human DNA polymerase eta with PCNA". Mol. Cell. Biol. 21 (21): 7199–206. doi:10.1128/MCB.21.21.7199-7206.2001. PMC 99895. PMID 11585903. 

Further reading[edit]

External links[edit]

This article incorporates text from the United States National Library of Medicine, which is in the public domain.