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'''DNA polymerase eta''' ('''Pol η'''), is a [[protein]] that in humans is encoded by the ''POLH'' [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: POLH polymerase (DNA directed), eta| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5429| accessdate = }}</ref><ref name="pmid10385124">{{cite journal | vauthors = Masutani C, Kusumoto R, Yamada A, Dohmae N, Yokoi M, Yuasa M, Araki M, Iwai S, Takio K, Hanaoka F | title = The XPV (xeroderma pigmentosum variant) gene encodes human DNA polymerase eta | journal = Nature | volume = 399 | issue = 6737 | pages = 700–4  | date = June 1999 | pmid = 10385124 | doi = 10.1038/21447 }}</ref><ref name="pmid10398605">{{cite journal | vauthors = Johnson RE, Kondratick CM, Prakash S, Prakash L | title = hRAD30 mutations in the variant form of xeroderma pigmentosum | journal = Science | volume = 285 | issue = 5425 | pages = 263–5  | date = July 1999 | pmid = 10398605 | doi = 10.1126/science.285.5425.263 | url = http://www.sciencemag.org/cgi/pmidlookup?view=long&pmid=10398605 }}</ref>


DNA polymerase eta is a eukaryotic [[DNA polymerase]] involved in the [[DNA repair#Translesion synthesis|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.


'''DNA polymerase eta''' ('''Pol η''') is a eukaryotic [[DNA polymerase]] involved in the [[DNA repair#Translesion synthesis|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 Variant.  Polymerase eta is particularly important for allowing accurate translesion synthesis of DNA damage resulting from ultraviolet radiation or UV. 
== Function ==


==References==
This gene encodes a member of the Y family of specialized [[DNA polymerase]]s. It copies undamaged DNA with a lower fidelity than other DNA-directed polymerases. However, it accurately replicates UV-damaged DNA; when [[thymine dimer]]s 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.<ref name="entrez"/>
{{refbegin}}
===Bypass of 8-oxoguanine===
* http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=retrieve&list_uids=5429
 
During [[DNA replication]] of the ''[[Saccharomyces cerevisiae]]'' [[chromosome]], the [[DNA oxidation|oxidative DNA damage]] [[8-oxoguanine]] triggers a switch to translesion synthesis by DNA polymerase eta.<ref name="pmid23935538">{{cite journal |vauthors=Rodriguez GP, Song JB, Crouse GF |title=In vivo bypass of 8-oxodG |journal=PLoS Genet. |volume=9 |issue=8 |pages=e1003682 |year=2013 |pmid=23935538 |pmc=3731214 |doi=10.1371/journal.pgen.1003682 |url=}}</ref>  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<ref name="pmid12405351">{{cite journal | vauthors = Stary A, Sarasin A | title = Molecular mechanisms of UV-induced mutations as revealed by the study of DNA polymerase eta in human cells | journal = Res. Microbiol. | volume = 153 | issue = 7 | pages = 441–5  | date = September 2002 | pmid = 12405351 | doi = 10.1016/S0923-2508(02)01343-8 | url = http://linkinghub.elsevier.com/retrieve/pii/S0923-2508(02)01343-8 }}</ref><ref name="pmid20012583">{{cite journal | vauthors = Cruet-Hennequart S, Gallagher K, Sokòl AM, Villalan S, Prendergast AM, Carty MP | title = DNA polymerase eta, a key protein in translesion synthesis in human cells | journal = Sub-cellular Biochemistry | volume = 50 | issue = | pages = 189–209 | year = 2010 | pmid = 20012583 | doi = 10.1007/978-90-481-3471-7_10 }}</ref>
 
== Interactions ==
 
POLH has been shown to [[Protein-protein interaction|interact]] with [[PCNA]].<ref name="pmid11585903">{{cite journal | vauthors = Haracska L, Johnson RE, Unk I, Phillips B, Hurwitz J, Prakash L, Prakash S | title = Physical and functional interactions of human DNA polymerase eta with PCNA | journal = Mol. Cell. Biol. | volume = 21 | issue = 21 | pages = 7199–206  | date = November 2001 | pmid = 11585903 | pmc = 99895 | doi = 10.1128/MCB.21.21.7199-7206.2001 }}</ref>
 
== References ==
{{Reflist}}
 
== Further reading ==  
{{refbegin | 2}}
* {{cite journal | vauthors =  Plachta M, Halas,  McIntyre J, Sledziewska-Gojska E | title = The steady-state level and stability of TLS polymerase eta are cellcycle dependent in the yeast S. cerevisiae | journal = DNA Repair | volume = 29 | pages = 147–153 | year = 2015 | doi = 10.1016/j.dnarep.2015.02.015 |PMID = 25766643 }}
* {{cite journal | vauthors = Skoneczna A, McIn Atyre J, Skoneczny M, Policinska Z, Sledziewska-Gojska E | title = Polymerase eta is a short-lived, proteasomally degraded protein that is temporarily stabilized following UV irradiation in Saccharomyces cerevisiae | journal = J. Mol. Biol. | volume = 366 | issue = 4 | pages = 1074–86 | year = 2007 | pmid = 17198712 | doi = 10.1016/j.jmb.2006.11.093 }}
* {{cite journal | vauthors = Masutani C, Kusumoto R, Yamada A, Dohmae N, Yokoi M, Yuasa M, Araki M, Iwai S, Takio K, Hanaoka F | title = The XPV (xeroderma pigmentosum variant) gene encodes human DNA polymerase eta | journal = Nature | volume = 399 | issue = 6737 | pages = 700–4 | year = 1999 | pmid = 10385124 | doi = 10.1038/21447 }}
* {{cite journal | vauthors = Johnson RE, Kondratick CM, Prakash S, Prakash L | title = hRAD30 mutations in the variant form of xeroderma pigmentosum | journal = Science | volume = 285 | issue = 5425 | pages = 263–5 | year = 1999 | pmid = 10398605 | doi = 10.1126/science.285.5425.263 }}
* {{cite journal | vauthors = Masutani C, Kusumoto R, Iwai S, Hanaoka F | title = Mechanisms of accurate translesion synthesis by human DNA polymerase eta | journal = EMBO J. | volume = 19 | issue = 12 | pages = 3100–9 | year = 2000 | pmid = 10856253 | pmc = 203367 | doi = 10.1093/emboj/19.12.3100 }}
* {{cite journal | vauthors = Yamada A, Masutani C, Iwai S, Hanaoka F | title = Complementation of defective translesion synthesis and UV light sensitivity in xeroderma pigmentosum variant cells by human and mouse DNA polymerase eta | journal = Nucleic Acids Res. | volume = 28 | issue = 13 | pages = 2473–80 | year = 2000 | pmid = 10871396 | pmc = 102698 | doi = 10.1093/nar/28.13.2473 }}
* {{cite journal | vauthors = Yuasa M, Masutani C, Eki T, Hanaoka F | title = Genomic structure, chromosomal localization and identification of mutations in the xeroderma pigmentosum variant (XPV) gene | journal = Oncogene | volume = 19 | issue = 41 | pages = 4721–8 | year = 2000 | pmid = 11032022 | doi = 10.1038/sj.onc.1203842 }}
* {{cite journal | vauthors = Itoh T, Linn S, Kamide R, Tokushige H, Katori N, Hosaka Y, Yamaizumi M | title = Xeroderma pigmentosum variant heterozygotes show reduced levels of recovery of replicative DNA synthesis in the presence of caffeine after ultraviolet irradiation | journal = J. Invest. Dermatol. | volume = 115 | issue = 6 | pages = 981–5 | year = 2000 | pmid = 11121129 | doi = 10.1046/j.1523-1747.2000.00154.x }}
* {{cite journal | vauthors = Zeng X, Winter DB, Kasmer C, Kraemer KH, Lehmann AR, Gearhart PJ | title = DNA polymerase eta is an A-T mutator in somatic hypermutation of immunoglobulin variable genes | journal = Nat. Immunol. | volume = 2 | issue = 6 | pages = 537–41 | year = 2001 | pmid = 11376341 | doi = 10.1038/88740 }}
* {{cite journal | vauthors = Matsuda T, Bebenek K, Masutani C, Rogozin IB, Hanaoka F, Kunkel TA | title = Error rate and specificity of human and murine DNA polymerase eta | journal = J. Mol. Biol. | volume = 312 | issue = 2 | pages = 335–46 | year = 2001 | pmid = 11554790 | doi = 10.1006/jmbi.2001.4937 }}
* {{cite journal | vauthors = Haracska L, Johnson RE, Unk I, Phillips B, Hurwitz J, Prakash L, Prakash S | title = Physical and functional interactions of human DNA polymerase eta with PCNA | journal = Mol. Cell. Biol. | volume = 21 | issue = 21 | pages = 7199–206 | year = 2001 | pmid = 11585903 | pmc = 99895 | doi = 10.1128/MCB.21.21.7199-7206.2001 }}
* {{cite journal | vauthors = Glick E, Vigna KL, Loeb LA | title = Mutations in human DNA polymerase eta motif II alter bypass of DNA lesions | journal = EMBO J. | volume = 20 | issue = 24 | pages = 7303–12 | year = 2001 | pmid = 11743006 | pmc = 125802 | doi = 10.1093/emboj/20.24.7303 }}
* {{cite journal | vauthors = Limoli CL, Giedzinski E, Bonner WM, Cleaver JE | title = UV-induced replication arrest in the xeroderma pigmentosum variant leads to DNA double-strand breaks, gamma -H2AX formation, and Mre11 relocalization | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 99 | issue = 1 | pages = 233–8 | year = 2002 | pmid = 11756691 | pmc = 117544 | doi = 10.1073/pnas.231611798 }}
* {{cite journal | vauthors = 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 | title = Molecular analysis of mutations in DNA polymerase eta in xeroderma pigmentosum-variant patients | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 99 | issue = 2 | pages = 815–20 | year = 2002 | pmid = 11773631 | pmc = 117388 | doi = 10.1073/pnas.022473899 }}
* {{cite journal | vauthors = Chiapperino D, Kroth H, Kramarczuk IH, Sayer JM, Masutani C, Hanaoka F, Jerina DM, Cheh AM | title = Preferential misincorporation of purine nucleotides by human DNA polymerase eta opposite benzo[a]pyrene 7,8-diol 9,10-epoxide deoxyguanosine adducts | journal = J. Biol. Chem. | volume = 277 | issue = 14 | pages = 11765–71 | year = 2002 | pmid = 11821420 | doi = 10.1074/jbc.M112139200 }}
* {{cite journal | vauthors = Kusumoto R, Masutani C, Iwai S, Hanaoka F | title = Translesion synthesis by human DNA polymerase eta across thymine glycol lesions | journal = Biochemistry | volume = 41 | issue = 19 | pages = 6090–9 | year = 2002 | pmid = 11994004 | doi = 10.1021/bi025549k }}
* {{cite journal | vauthors = Yavuz S, Yavuz AS, Kraemer KH, Lipsky PE | title = The role of polymerase eta in somatic hypermutation determined by analysis of mutations in a patient with xeroderma pigmentosum variant | journal = J. Immunol. | volume = 169 | issue = 7 | pages = 3825–30 | year = 2002 | pmid = 12244178 | doi = 10.4049/jimmunol.169.7.3825 }}
* {{cite journal | vauthors = Kannouche P, Fernández de Henestrosa AR, Coull B, Vidal AE, Gray C, Zicha D, Woodgate R, Lehmann AR | title = Localization of DNA polymerases eta and iota to the replication machinery is tightly co-ordinated in human cells | journal = EMBO J. | volume = 21 | issue = 22 | pages = 6246–56 | year = 2002 | pmid = 12426396 | pmc = 137208 | doi = 10.1093/emboj/cdf618 }}
* {{cite journal | vauthors = Zheng H, Wang X, Warren AJ, Legerski RJ, Nairn RS, Hamilton JW, Li L | title = Nucleotide excision repair- and polymerase eta-mediated error-prone removal of mitomycin C interstrand cross-links | journal = Mol. Cell. Biol. | volume = 23 | issue = 2 | pages = 754–61 | year = 2003 | pmid = 12509472 | pmc = 151552 | doi = 10.1128/MCB.23.2.754-761.2003 }}
* {{cite journal | vauthors = Yang IY, Miller H, Wang Z, Frank EG, Ohmori H, Hanaoka F, Moriya M | title = Mammalian translesion DNA synthesis across an acrolein-derived deoxyguanosine adduct. Participation of DNA polymerase eta in error-prone synthesis in human cells | journal = J. Biol. Chem. | volume = 278 | issue = 16 | pages = 13989–94 | year = 2003 | pmid = 12584190 | doi = 10.1074/jbc.M212535200 }}
* {{cite journal | vauthors = Kannouche P, Fernández de Henestrosa AR, Coull B, Vidal AE, Gray C, Zicha D, Woodgate R, Lehmann AR | title = Localization of DNA polymerases eta and iota to the replication machinery is tightly co-ordinated in human cells | journal = EMBO J. | volume = 22 | issue = 5 | pages = 1223–33 | year = 2003 | pmid = 12606586 | pmc = 150329 | doi = 10.1093/emboj/cdf618 }}
{{refend}}
{{refend}}


== External links ==
* [https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=xp  GeneReviews/NIH/NCBI/UW entry on Xeroderma Pigmentosum]


{{PDB Gallery|geneid=5429}}
{{NLM content}}


[[Category:DNA replication]]
[[Category:DNA replication]]
 
[[Category:DNA-binding proteins]]
{{WH}}
{{WS}}

Latest revision as of 19:21, 5 September 2018

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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]

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.[4] 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[5][6]

Interactions

POLH has been shown to interact with PCNA.[7]

References

  1. ↑ 1.0 1.1 "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. ↑ 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.
  5. ↑ 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.
  6. ↑ Cruet-Hennequart S, Gallagher K, Sokòl AM, Villalan S, Prendergast AM, Carty MP (2010). "DNA polymerase eta, a key protein in translesion synthesis in human cells". Sub-cellular Biochemistry. 50: 189–209. doi:10.1007/978-90-481-3471-7_10. PMID 20012583.
  7. ↑ 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

External links

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

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