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.
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. Mutations in this gene result in XPV, a variant type of xeroderma pigmentosum.
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
^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. PMID10385124.
Plachta M, Halas, McIntyre J, Sledziewska-Gojska E (2015). "The steady-state level and stability of TLS polymerase eta are cellcycle dependent in the yeast S. cerevisiae". DNA Repair. 29: 147–153. doi:10.1016/j.dnarep.2015.02.015. PMID25766643.
Skoneczna A, McIn Atyre 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. PMID17198712.
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. PMID10385124.
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. PMID11032022.
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. PMID11121129.
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. PMID11376341.
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. PMID11554790.
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. PMID11821420.
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. PMID11994004.
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. PMID12244178.
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. PMID12584190.