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Tang, P. WRN Gene. Encyclopedia. Available online: https://encyclopedia.pub/entry/4625 (accessed on 20 April 2024).
Tang P. WRN Gene. Encyclopedia. Available at: https://encyclopedia.pub/entry/4625. Accessed April 20, 2024.
Tang, Peter. "WRN Gene" Encyclopedia, https://encyclopedia.pub/entry/4625 (accessed April 20, 2024).
Tang, P. (2020, December 24). WRN Gene. In Encyclopedia. https://encyclopedia.pub/entry/4625
Tang, Peter. "WRN Gene." Encyclopedia. Web. 24 December, 2020.
WRN Gene
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This entry is adapted from the peer-reviewed paper https://medlineplus.gov/genetics/gene/wrn

Werner syndrome RecQ like helicase: 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.

genes

1. Normal Function

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).

2. Health Conditions Related to Genetic Changes

2.1. 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.

2.2. Prostate cancer

2.3. 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.

3. Other Names for This Gene

  • RECQ3

  • RECQL2

  • RECQL3

  • Werner syndrome

  • Werner Syndrome helicase

  • Werner syndrome protein

  • Werner syndrome, RecQ helicase-like

  • WRN_HUMAN

References

  1. 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 genein human cancer. Proc Natl Acad Sci U S A. 2006 Jun 6;103(23):8822-7.
  2. Cheng WH, Muftuoglu M, Bohr VA. Werner syndrome protein: functions in theresponse to DNA damage and replication stress in S-phase. Exp Gerontol. 2007Sep;42(9):871-8.
  3. Comai L, Li B. The Werner syndrome protein at the crossroads of DNA repair andapoptosis. Mech Ageing Dev. 2004 Aug;125(8):521-8. Review.
  4. 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 cancercells. Cancer Sci. 2008 May;99(5):843-8. doi: 10.1111/j.1349-7006.2008.00778.x.
  5. 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-CordiscoE, 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 inWerner syndrome patients. Hum Mutat. 2006 Jun;27(6):558-67.
  6. Kudlow BA, Kennedy BK, Monnat RJ Jr. Werner and Hutchinson-Gilford progeriasyndromes: mechanistic basis of human progeroid diseases. Nat Rev Mol Cell Biol. 2007 May;8(5):394-404. Review.
  7. 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. Review.
  8. Monnat RJ Jr, Saintigny Y. Werner syndrome protein--unwinding function toexplain disease. Sci Aging Knowledge Environ. 2004 Mar 31;2004(13):re3. Review.
  9. Opresko PL, Calvo JP, von Kobbe C. Role for the Werner syndrome protein in thepromotion of tumor cell growth. Mech Ageing Dev. 2007 Jul-Aug;128(7-8):423-36.
  10. Oshima J, Martin GM, Hisama FM. Werner Syndrome. 2002 Dec 2 [updated 2016 Sep 29]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K,Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University ofWashington, Seattle; 1993-2020. Available fromhttp://www.ncbi.nlm.nih.gov/books/NBK1514/
  11. Ozgenc A, Loeb LA. Current advances in unraveling the function of the Wernersyndrome protein. Mutat Res. 2005 Sep 4;577(1-2):237-51. Review.
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Subjects: Genetics & Heredity
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Peter Tang
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Update Date: 24 Dec 2020
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