DNA polymerase eta

Polymerase (DNA directed), eta
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 List of PDB id codes 2I5O​, 2LSK​, 3MR2​, 3MR3​, 3MR5​, 3MR6​, 3SI8​, 3TQ1​, 4DL2​, 4DL3​, 4DL4​, 4DL5​, 4DL6​, 4DL7​, 4ECQ​, 4ECR​, 4ECS​, 4ECT​, 4ECU​, 4ECV​, 4ECW​, 4ECX​, 4ECY​, 4ECZ​, 4ED0​, 4ED1​, 4ED2​, 4ED3​, 4ED6​, 4ED7​, 4ED8​, 4EEY​, 4J9K​, 4J9L​, 4J9M​, 4J9N​, 4J9O​, 4J9P​, 4J9Q​, 4J9R​, 4J9S​, 4O3N​, 4O3O​, 4O3P​, 4O3Q​, 4O3R​, 4O3S​, 4Q8E​, 4Q8F​, 4RNM​, 4RNN​, 4RNO​, 4YP3​, 4YQW​, 4YR0​, 4YR2​, 4YR3​
Identifiers
Symbols	POLH ; RAD30; RAD30A; XP-V; XPV
External IDs	OMIM: 603968 MGI: 1891457 HomoloGene: 38189 ChEMBL: 5542 GeneCards: POLH Gene
EC number	2.7.7.7
Gene ontology Molecular function • damaged DNA binding • DNA-directed DNA polymerase activity • protein binding • metal ion binding Cellular component • nucleoplasm • cytoplasm Biological process • DNA synthesis involved in DNA repair • DNA replication • DNA repair • regulation of DNA repair • pyrimidine dimer repair • response to UV-C • translesion synthesis • error-free translesion synthesis • cellular response to UV-C Sources: Amigo / QuickGO
RNA expression pattern
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: 43.58 – 43.62 Mb	Chr 17: 46.17 – 46.2 Mb
PubMed search

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

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

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

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

References

1. "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

• Skoneczna A, McIntyre J, Skoneczny M, Policinska Z, Sledziewska-Gojska E (2007). "Polymerase eta is a short-lived, proteasomally degraded protein that is temporarily stabilized following UV irradiation in Saccharomyces cerevisiae". J. Mol. Biol. 366 (4): 1074–86. doi:10.1016/j.jmb.2006.11.093. PMID 17198712.
• Masutani C, Kusumoto R, Yamada A, Dohmae N, Yokoi M, Yuasa M, Araki M, Iwai S, Takio K, Hanaoka F (1999). "The XPV (xeroderma pigmentosum variant) gene encodes human DNA polymerase eta". Nature 399 (6737): 700–4. doi:10.1038/21447. PMID 10385124.
• Johnson RE, Kondratick CM, Prakash S, Prakash L (1999). "hRAD30 mutations in the variant form of xeroderma pigmentosum". Science 285 (5425): 263–5. doi:10.1126/science.285.5425.263. PMID 10398605.
• Masutani C, Kusumoto R, Iwai S, Hanaoka F (2000). "Mechanisms of accurate translesion synthesis by human DNA polymerase eta". EMBO J. 19 (12): 3100–9. doi:10.1093/emboj/19.12.3100. PMC 203367. PMID 10856253.
• Yamada A, Masutani C, Iwai S, Hanaoka F (2000). "Complementation of defective translesion synthesis and UV light sensitivity in xeroderma pigmentosum variant cells by human and mouse DNA polymerase eta". Nucleic Acids Res. 28 (13): 2473–80. doi:10.1093/nar/28.13.2473. PMC 102698. PMID 10871396.
• Yuasa M, Masutani C, Eki T, Hanaoka F (2000). "Genomic structure, chromosomal localization and identification of mutations in the xeroderma pigmentosum variant (XPV) gene". Oncogene 19 (41): 4721–8. doi:10.1038/sj.onc.1203842. PMID 11032022.
• Itoh T, Linn S, Kamide R, Tokushige H, Katori N, Hosaka Y, Yamaizumi M (2000). "Xeroderma pigmentosum variant heterozygotes show reduced levels of recovery of replicative DNA synthesis in the presence of caffeine after ultraviolet irradiation". J. Invest. Dermatol. 115 (6): 981–5. doi:10.1046/j.1523-1747.2000.00154.x. PMID 11121129.
• Zeng X, Winter DB, Kasmer C, Kraemer KH, Lehmann AR, Gearhart PJ (2001). "DNA polymerase eta is an A-T mutator in somatic hypermutation of immunoglobulin variable genes". Nat. Immunol. 2 (6): 537–41. doi:10.1038/88740. PMID 11376341.
• Matsuda T, Bebenek K, Masutani C, Rogozin IB, Hanaoka F, Kunkel TA (2001). "Error rate and specificity of human and murine DNA polymerase eta". J. Mol. Biol. 312 (2): 335–46. doi:10.1006/jmbi.2001.4937. PMID 11554790.
• Haracska L, Johnson RE, Unk I, Phillips B, Hurwitz J, Prakash L, Prakash S (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.
• Glick E, Vigna KL, Loeb LA (2001). "Mutations in human DNA polymerase eta motif II alter bypass of DNA lesions". EMBO J. 20 (24): 7303–12. doi:10.1093/emboj/20.24.7303. PMC 125802. PMID 11743006.
• Limoli CL, Giedzinski E, Bonner WM, Cleaver JE (2002). "UV-induced replication arrest in the xeroderma pigmentosum variant leads to DNA double-strand breaks, gamma -H2AX formation, and Mre11 relocalization". Proc. Natl. Acad. Sci. U.S.A. 99 (1): 233–8. doi:10.1073/pnas.231611798. PMC 117544. PMID 11756691.
• Broughton BC, Cordonnier A, Kleijer WJ, Jaspers NG, Fawcett H, Raams A, Garritsen VH, Stary A, Avril MF, Boudsocq F, Masutani C, Hanaoka F, Fuchs RP, Sarasin A, Lehmann AR (2002). "Molecular analysis of mutations in DNA polymerase eta in xeroderma pigmentosum-variant patients". Proc. Natl. Acad. Sci. U.S.A. 99 (2): 815–20. doi:10.1073/pnas.022473899. PMC 117388. PMID 11773631.
• Chiapperino D, Kroth H, Kramarczuk IH, Sayer JM, Masutani C, Hanaoka F, Jerina DM, Cheh AM (2002). "Preferential misincorporation of purine nucleotides by human DNA polymerase eta opposite benzo[a]pyrene 7,8-diol 9,10-epoxide deoxyguanosine adducts". J. Biol. Chem. 277 (14): 11765–71. doi:10.1074/jbc.M112139200. PMID 11821420.
• Kusumoto R, Masutani C, Iwai S, Hanaoka F (2002). "Translesion synthesis by human DNA polymerase eta across thymine glycol lesions". Biochemistry 41 (19): 6090–9. doi:10.1021/bi025549k. PMID 11994004.
• Yavuz S, Yavuz AS, Kraemer KH, Lipsky PE (2002). "The role of polymerase eta in somatic hypermutation determined by analysis of mutations in a patient with xeroderma pigmentosum variant". J. Immunol. 169 (7): 3825–30. doi:10.4049/jimmunol.169.7.3825. PMID 12244178.
• Kannouche P, Fernández de Henestrosa AR, Coull B, Vidal AE, Gray C, Zicha D, Woodgate R, Lehmann AR (2002). "Localization of DNA polymerases eta and iota to the replication machinery is tightly co-ordinated in human cells". EMBO J. 21 (22): 6246–56. doi:10.1093/emboj/cdf618. PMC 137208. PMID 12426396.
• Zheng H, Wang X, Warren AJ, Legerski RJ, Nairn RS, Hamilton JW, Li L (2003). "Nucleotide excision repair- and polymerase eta-mediated error-prone removal of mitomycin C interstrand cross-links". Mol. Cell. Biol. 23 (2): 754–61. doi:10.1128/MCB.23.2.754-761.2003. PMC 151552. PMID 12509472.
• Yang IY, Miller H, Wang Z, Frank EG, Ohmori H, Hanaoka F, Moriya M (2003). "Mammalian translesion DNA synthesis across an acrolein-derived deoxyguanosine adduct. Participation of DNA polymerase eta in error-prone synthesis in human cells". J. Biol. Chem. 278 (16): 13989–94. doi:10.1074/jbc.M212535200. PMID 12584190.
• Kannouche P, Fernández de Henestrosa AR, Coull B, Vidal AE, Gray C, Zicha D, Woodgate R, Lehmann AR (2003). "Localization of DNA polymerases eta and iota to the replication machinery is tightly co-ordinated in human cells". EMBO J. 22 (5): 1223–33. doi:10.1093/emboj/cdf618. PMC 150329. PMID 12606586.

External links

• GeneReviews/NIH/NCBI/UW entry on Xeroderma Pigmentosum

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