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Normal Function
The POLH gene provides instructions for making a protein called DNA polymerase eta. DNA polymerases are a group of enzymes that "read" sequences of DNA and use them as templates to produce new DNA. These enzymes are important for copying (replicating) cells' genetic material in preparation for cell division. DNA polymerases also play critical roles in DNA repair.
The major function of DNA polymerase eta is to replicate DNA that has been damaged, particularly by ultraviolet (UV) rays from sunlight. Most other DNA polymerases are unable to replicate DNA with this type of damage. When they reach a segment of damaged DNA, they get stuck and the replication process stalls. However, when DNA polymerase eta encounters damaged DNA, it skips over the abnormal segment and continues copying. This activity, which is known as translesion synthesis, allows cells to tolerate some abnormalities created by UV exposure. Without this tolerance, unrepaired DNA damage would block DNA replication and cause the cell to die. Therefore, DNA polymerase eta plays an essential role in protecting cells from some of the effects of DNA damage.
DNA polymerase eta is a relatively "error-prone" polymerase. When it bypasses damaged DNA, it often inserts an incorrect DNA building block (nucleotide). This type of error results in a variant (also called a mutation) in the replicated DNA.
Health Conditions Related to Genetic Changes
Xeroderma pigmentosum
Several variants in the POLH gene have been found to cause a condition called xeroderma pigmentosum. In particular, POLH gene variants cause the variant type of xeroderma pigmentosum (XP-V). Like the other forms of xeroderma pigmentosum, XP-V is characterized by an increased sensitivity to UV rays from sunlight. However, this form of the disorder is typically not associated with neurological abnormalities, such as delayed development and hearing loss.
Most POLH gene variants prevent the production of any detectable DNA polymerase eta. A loss of this enzyme prevents cells from replicating damaged DNA effectively. Without this mechanism for tolerating DNA damage, errors resulting from exposure to UV rays accumulate in genes that control cell growth and division. These errors cause cells to grow too fast and in an uncontrolled way. As a result, people with XP-V have an increased risk of developing skin cancer in areas where the skin is exposed to sunlight.
More About This Health ConditionOther Names for This Gene
- FLJ16395
- FLJ21978
- POLH_HUMAN
- polymerase (DNA directed), eta
- polymerase (DNA) eta
- RAD30
- RAD30 homolog A
- RAD30A
- xeroderma pigmentosum variant type protein
- XP-V
- XPV
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- 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. Molecular analysis of mutations in DNA polymerase eta in xeroderma pigmentosum-variant patients. Proc Natl Acad Sci U S A. 2002 Jan 22;99(2):815-20. doi: 10.1073/pnas.022473899. Epub 2002 Jan 2. Citation on PubMed or Free article on PubMed Central
- Inui H, Oh KS, Nadem C, Ueda T, Khan SG, Metin A, Gozukara E, Emmert S, Slor H, Busch DB, Baker CC, DiGiovanna JJ, Tamura D, Seitz CS, Gratchev A, Wu WH, Chung KY, Chung HJ, Azizi E, Woodgate R, Schneider TD, Kraemer KH. Xeroderma pigmentosum-variant patients from America, Europe, and Asia. J Invest Dermatol. 2008 Aug;128(8):2055-68. doi: 10.1038/jid.2008.48. Epub 2008 Mar 27. Citation on PubMed or Free article on PubMed Central
- Johnson RE, Kondratick CM, Prakash S, Prakash L. hRAD30 mutations in the variant form of xeroderma pigmentosum. Science. 1999 Jul 9;285(5425):263-5. doi: 10.1126/science.285.5425.263. Citation on PubMed
- Masutani C, Kusumoto R, Yamada A, Dohmae N, Yokoi M, Yuasa M, Araki M, Iwai S, Takio K, Hanaoka F. The XPV (xeroderma pigmentosum variant) gene encodes human DNA polymerase eta. Nature. 1999 Jun 17;399(6737):700-4. doi: 10.1038/21447. Citation on PubMed
- Tanioka M, Masaki T, Ono R, Nagano T, Otoshi-Honda E, Matsumura Y, Takigawa M, Inui H, Miyachi Y, Moriwaki S, Nishigori C. Molecular analysis of DNA polymerase eta gene in Japanese patients diagnosed as xeroderma pigmentosum variant type. J Invest Dermatol. 2007 Jul;127(7):1745-51. doi: 10.1038/sj.jid.5700759. Epub 2007 Mar 8. Citation on PubMed
- Waters LS, Minesinger BK, Wiltrout ME, D'Souza S, Woodruff RV, Walker GC. Eukaryotic translesion polymerases and their roles and regulation in DNA damage tolerance. Microbiol Mol Biol Rev. 2009 Mar;73(1):134-54. doi: 10.1128/MMBR.00034-08. Citation on PubMed or Free article on PubMed Central
- Yuasa M, Masutani C, Eki T, Hanaoka F. Genomic structure, chromosomal localization and identification of mutations in the xeroderma pigmentosum variant (XPV) gene. Oncogene. 2000 Sep 28;19(41):4721-8. doi: 10.1038/sj.onc.1203842. Citation on PubMed
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