DNA polymerase eta

DNA polymerase eta (Pol η), is a protein that in humans is encoded by the POLH gene.[5][6][7]

POLH
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesPOLH, RAD30, RAD30A, XP-V, XPV, DNA polymerase eta, polymerase (DNA) eta
External IDsOMIM: 603968 MGI: 1891457 HomoloGene: 38189 GeneCards: POLH
Orthologs
SpeciesHumanMouse
Entrez

5429

80905

Ensembl

ENSG00000170734

ENSMUSG00000023953

UniProt

Q9Y253

Q9JJN0

RefSeq (mRNA)

NM_001291969
NM_001291970
NM_006502

NM_030715
NM_001364947

RefSeq (protein)

NP_001278898
NP_001278899
NP_006493

NP_109640
NP_001351876

Location (UCSC)Chr 6: 43.58 – 43.62 MbChr 17: 46.48 – 46.51 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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

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.[5]

Bypass of 8-oxoguanine

During DNA replication of the Saccharomyces cerevisiae chromosome, the oxidative DNA damage 8-oxoguanine triggers a switch to translesion synthesis by DNA polymerase eta.[8] This polymerase replicates 8-oxoguanine with an accuracy (insertion of a cytosine opposite the 8-oxoguanine) of approximately 94%. Replication of 8-oxoguanine in the absence of DNA polymerase eta is less than 40%.

Clinical significance

Mutations in this gene result in XPV, a variant type of xeroderma pigmentosum, characterized by sun sensitivity, elevated incidence of skin cancer, and at the cellular level, by delayed replication and hypermutability after UV-irradiation[9][10]

Interactions

POLH has been shown to interact with PCNA.[11]

References

  1. GRCh38: Ensembl release 89: ENSG00000170734 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000023953 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. "Entrez Gene: POLH polymerase (DNA directed), eta".
  6. 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. Bibcode:1999Natur.399..700M. doi:10.1038/21447. PMID 10385124. S2CID 4429698.
  7. 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.
  8. Rodriguez GP, Song JB, Crouse GF (2013). "In vivo bypass of 8-oxodG". PLOS Genet. 9 (8): e1003682. doi:10.1371/journal.pgen.1003682. PMC 3731214. PMID 23935538.
  9. 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.
  10. Cruet-Hennequart S, Gallagher K, Sokòl AM, Villalan S, Prendergast AM, Carty MP (2010). "DNA Polymerase η, a Key Protein in Translesion Synthesis in Human Cells". DNA polymerase eta, a key protein in translesion synthesis in human cells. Subcellular Biochemistry. Vol. 50. pp. 189–209. doi:10.1007/978-90-481-3471-7_10. ISBN 978-90-481-3470-0. PMID 20012583.
  11. 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

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