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WRN gene
URL of this page: https://medlineplus.gov/genetics/gene/wrn/

WRN gene

WRN RecQ like helicase

Normal Function

The WRN gene provides instructions for producing the Werner protein, which plays a critical role in repairing damaged DNA. The Werner protein functions as a type of enzyme called a helicase. Helicase enzymes generally unwind and separate double-stranded DNA. The Werner protein also functions as an enzyme called an exonuclease. Exonucleases trim the broken ends of damaged DNA by removing DNA building blocks (nucleotides). Research suggests that the Werner protein first unwinds the DNA and then removes abnormal DNA structures that have been accidentally generated.

Overall, the Werner protein helps maintain the structure and integrity of a person's DNA. This protein plays an important role in copying (replicating) DNA before cell division and transferring the information in genes to the cell machinery that makes proteins (transcription). Additionally, recent studies suggest that the Werner protein may be particularly important for maintaining DNA at the ends of chromosomes (telomeres).

Health Conditions Related to Genetic Changes

Werner syndrome

More than 60 mutations in the WRN gene are known to cause Werner syndrome. Most of these mutations result in an abnormally short, nonfunctional Werner protein. Research suggests that this shortened protein is not transported into the cell's nucleus, where it normally interacts with DNA. Furthermore, the shortened protein is broken down more quickly than the normal Werner protein, reducing the amount of this protein in the cell. Without normal Werner protein in the nucleus, DNA replication, repair, and transcription are disrupted. Researchers are still determining how mutations in the WRN gene lead to the signs and symptoms of Werner syndrome.

More About This Health Condition

Prostate cancer

MedlinePlus Genetics provides information about Prostate cancer

More About This Health Condition

Cancers

Some changes to a person's genes are acquired during that person's lifetime and are present only in certain cells. These differences, called somatic changes, are not inherited. Somatic changes in the WRN gene are found in nonhereditary tumors and involve a process called methylation. Methylation is a chemical modification that attaches small molecules called methyl groups to certain segments of DNA. When too many methyl groups are attached to the WRN gene (hypermethylation), the gene is turned off and the Werner protein is not produced. Without this protein, cells do not respond normally to DNA damage. The lack of Werner protein allows mutations to accumulate in other genes, which may cause cells to grow and divide in an uncontrolled way. This kind of unregulated cell growth can lead to the formation of cancerous tumors. Hypermethylation of the WRN gene has been found in many different types of tumors, including colon, rectal, lung, stomach, prostate, breast, and thyroid tumors.

Other Names for This Gene

  • RECQ3
  • RECQL2
  • RECQL3
  • Werner syndrome
  • Werner Syndrome helicase
  • Werner syndrome protein
  • Werner syndrome, RecQ helicase-like
  • WRN_HUMAN

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Catalog of Genes and Diseases from OMIM

Gene and Variant Databases

References

  • Agrelo R, Cheng WH, Setien F, Ropero S, Espada J, Fraga MF, Herranz M, Paz MF, Sanchez-Cespedes M, Artiga MJ, Guerrero D, Castells A, von Kobbe C, Bohr VA, Esteller M. Epigenetic inactivation of the premature aging Werner syndrome gene in human cancer. Proc Natl Acad Sci U S A. 2006 Jun 6;103(23):8822-7. doi: 10.1073/pnas.0600645103. Epub 2006 May 24. Citation on PubMed or Free article on PubMed Central
  • Cheng WH, Muftuoglu M, Bohr VA. Werner syndrome protein: functions in the response to DNA damage and replication stress in S-phase. Exp Gerontol. 2007 Sep;42(9):871-8. doi: 10.1016/j.exger.2007.04.011. Epub 2007 May 10. Citation on PubMed
  • Comai L, Li B. The Werner syndrome protein at the crossroads of DNA repair and apoptosis. Mech Ageing Dev. 2004 Aug;125(8):521-8. doi: 10.1016/j.mad.2004.06.004. Citation on PubMed
  • Futami K, Ishikawa Y, Goto M, Furuichi Y, Sugimoto M. Role of Werner syndrome gene product helicase in carcinogenesis and in resistance to genotoxins by cancer cells. Cancer Sci. 2008 May;99(5):843-8. doi: 10.1111/j.1349-7006.2008.00778.x. Epub 2008 Feb 26. Citation on PubMed
  • Huang S, Lee L, Hanson NB, Lenaerts C, Hoehn H, Poot M, Rubin CD, Chen DF, Yang CC, Juch H, Dorn T, Spiegel R, Oral EA, Abid M, Battisti C, Lucci-Cordisco E, Neri G, Steed EH, Kidd A, Isley W, Showalter D, Vittone JL, Konstantinow A, Ring J, Meyer P, Wenger SL, von Herbay A, Wollina U, Schuelke M, Huizenga CR, Leistritz DF, Martin GM, Mian IS, Oshima J. The spectrum of WRN mutations in Werner syndrome patients. Hum Mutat. 2006 Jun;27(6):558-67. doi: 10.1002/humu.20337. Citation on PubMed or Free article on PubMed Central
  • Kudlow BA, Kennedy BK, Monnat RJ Jr. Werner and Hutchinson-Gilford progeria syndromes: mechanistic basis of human progeroid diseases. Nat Rev Mol Cell Biol. 2007 May;8(5):394-404. doi: 10.1038/nrm2161. Citation on PubMed
  • Lee JW, Harrigan J, Opresko PL, Bohr VA. Pathways and functions of the Werner syndrome protein. Mech Ageing Dev. 2005 Jan;126(1):79-86. doi: 10.1016/j.mad.2004.09.011. Citation on PubMed
  • Monnat RJ Jr, Saintigny Y. Werner syndrome protein--unwinding function to explain disease. Sci Aging Knowledge Environ. 2004 Mar 31;2004(13):re3. doi: 10.1126/sageke.2004.13.re3. Citation on PubMed
  • Opresko PL, Calvo JP, von Kobbe C. Role for the Werner syndrome protein in the promotion of tumor cell growth. Mech Ageing Dev. 2007 Jul-Aug;128(7-8):423-36. doi: 10.1016/j.mad.2007.05.009. Epub 2007 May 31. Citation on PubMed
  • Oshima J, Martin GM, Hisama FM. Werner Syndrome. 2002 Dec 2 [updated 2021 May 13]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Available from http://www.ncbi.nlm.nih.gov/books/NBK1514/ Citation on PubMed
  • Ozgenc A, Loeb LA. Current advances in unraveling the function of the Werner syndrome protein. Mutat Res. 2005 Sep 4;577(1-2):237-51. doi: 10.1016/j.mrfmmm.2005.03.020. Citation on PubMed

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