Biology:DNA polymerase eta

Short description: Protein-coding gene in the species Homo sapiens

Generic protein structure example

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

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.

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. 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

Interactions

POLH has been shown to interact with PCNA.

Further reading

• "The steady-state level and stability of TLS polymerase eta are cellcycle dependent in the yeast S. cerevisiae". DNA Repair 29: 147–153. 2015. doi:10.1016/j.dnarep.2015.02.015. PMID 25766643. http://eprints.ibb.waw.pl/954/1/Pol%20eta%20revision%20final.doc. 
• "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. 2007. doi:10.1016/j.jmb.2006.11.093. PMID 17198712. 
• "The XPV (xeroderma pigmentosum variant) gene encodes human DNA polymerase eta". Nature 399 (6737): 700–4. 1999. doi:10.1038/21447. PMID 10385124. Bibcode: 1999Natur.399..700M. 
• "hRAD30 mutations in the variant form of xeroderma pigmentosum". Science 285 (5425): 263–5. 1999. doi:10.1126/science.285.5425.263. PMID 10398605. 
• "Mechanisms of accurate translesion synthesis by human DNA polymerase eta". EMBO J. 19 (12): 3100–9. 2000. doi:10.1093/emboj/19.12.3100. PMID 10856253. 
• "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. 2000. doi:10.1093/nar/28.13.2473. PMID 10871396. 
• "Genomic structure, chromosomal localization and identification of mutations in the xeroderma pigmentosum variant (XPV) gene". Oncogene 19 (41): 4721–8. 2000. doi:10.1038/sj.onc.1203842. PMID 11032022. 
• "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. 2000. doi:10.1046/j.1523-1747.2000.00154.x. PMID 11121129. 
• "DNA polymerase eta is an A-T mutator in somatic hypermutation of immunoglobulin variable genes". Nat. Immunol. 2 (6): 537–41. 2001. doi:10.1038/88740. PMID 11376341. 
• "Error rate and specificity of human and murine DNA polymerase eta". J. Mol. Biol. 312 (2): 335–46. 2001. doi:10.1006/jmbi.2001.4937. PMID 11554790. https://zenodo.org/record/1229894. 
• "Physical and functional interactions of human DNA polymerase eta with PCNA". Mol. Cell. Biol. 21 (21): 7199–206. 2001. doi:10.1128/MCB.21.21.7199-7206.2001. PMID 11585903. 
• "Mutations in human DNA polymerase eta motif II alter bypass of DNA lesions". EMBO J. 20 (24): 7303–12. 2001. doi:10.1093/emboj/20.24.7303. PMID 11743006. 
• "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. 2002. doi:10.1073/pnas.231611798. PMID 11756691. Bibcode: 2002PNAS...99..233L. 
• "Molecular analysis of mutations in DNA polymerase eta in xeroderma pigmentosum-variant patients". Proc. Natl. Acad. Sci. U.S.A. 99 (2): 815–20. 2002. doi:10.1073/pnas.022473899. PMID 11773631. Bibcode: 2002PNAS...99..815B. 
• "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. 2002. doi:10.1074/jbc.M112139200. PMID 11821420. 
• "Translesion synthesis by human DNA polymerase eta across thymine glycol lesions". Biochemistry 41 (19): 6090–9. 2002. doi:10.1021/bi025549k. PMID 11994004. 
• "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. 2002. doi:10.4049/jimmunol.169.7.3825. PMID 12244178. 
• "Localization of DNA polymerases eta and iota to the replication machinery is tightly co-ordinated in human cells". EMBO J. 21 (22): 6246–56. 2002. doi:10.1093/emboj/cdf618. PMID 12426396. 
• "Nucleotide excision repair- and polymerase eta-mediated error-prone removal of mitomycin C interstrand cross-links". Mol. Cell. Biol. 23 (2): 754–61. 2003. doi:10.1128/MCB.23.2.754-761.2003. PMID 12509472. 
• "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. 2003. doi:10.1074/jbc.M212535200. PMID 12584190. 
• "Localization of DNA polymerases eta and iota to the replication machinery is tightly co-ordinated in human cells". EMBO J. 22 (5): 1223–33. 2003. doi:10.1093/emboj/cdf618. 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.