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Genetics Home Reference: your guide to understanding genetic conditions
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POLH

Reviewed May 2010

What is the official name of the POLH gene?

The official name of this gene is “polymerase (DNA directed), eta.”

POLH is the gene's official symbol. The POLH gene is also known by other names, listed below.

What is the normal function of the POLH gene?

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 mutation in the replicated DNA.

How are changes in the POLH gene related to health conditions?

xeroderma pigmentosum - caused by mutations in the POLH gene

More than 30 mutations in the POLH gene have been found to 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 mutations 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.

Where is the POLH gene located?

Cytogenetic Location: 6p21.1

Molecular Location on chromosome 6: base pairs 43,576,140 to 43,620,522

The POLH gene is located on the short (p) arm of chromosome 6 at position 21.1.

The POLH gene is located on the short (p) arm of chromosome 6 at position 21.1.

More precisely, the POLH gene is located from base pair 43,576,140 to base pair 43,620,522 on chromosome 6.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about POLH?

You and your healthcare professional may find the following resources about POLH helpful.

You may also be interested in these resources, which are designed for genetics professionals and researchers.

What other names do people use for the POLH gene or gene products?

  • DNA polymerase eta
  • FLJ16395
  • FLJ21978
  • POLH_HUMAN
  • RAD30
  • RAD30A
  • RAD30 homolog A
  • xeroderma pigmentosum variant type protein
  • XPV
  • XP-V

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding POLH?

cancer ; cell ; cell division ; DNA ; DNA damage ; DNA repair ; DNA replication ; enzyme ; gene ; mutation ; neurological ; nucleotide ; protein ; sensitivity ; synthesis ; UV rays

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/glossary).

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. Epub 2002 Jan 2. (http://www.ncbi.nlm.nih.gov/pubmed/11773631?dopt=Abstract)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/18368133?dopt=Abstract)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/10398605?dopt=Abstract)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/10385124?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/5429)
  • 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. Epub 2007 Mar 8. (http://www.ncbi.nlm.nih.gov/pubmed/17344931?dopt=Abstract)
  • 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. Review. (http://www.ncbi.nlm.nih.gov/pubmed/19258535?dopt=Abstract)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/11032022?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: May 2010
Published: December 22, 2014