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DKC1 gene

dyskerin pseudouridine synthase 1
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Normal Function

The DKC1 gene provides instructions for making a protein called dyskerin. This protein is involved in maintaining structures called telomeres, which are found at the ends of chromosomes. Telomeres help protect chromosomes from abnormally sticking together or breaking down (degrading).

In most cells, telomeres become progressively shorter as the cell divides. After a certain number of cell divisions, the telomeres become so short that they trigger the cell to stop dividing or to self-destruct (undergo apoptosis).

Telomeres are maintained by two important protein complexes, telomerase and shelterin. Telomerase counteracts the shortening of telomeres by adding small repeated segments of DNA to the ends of chromosomes each time the cell divides. One component of telomerase, called hTR, provides a template for creating the repeated sequence of DNA that telomerase adds to the ends of chromosomes. The dyskerin protein attaches (binds) to hTR and helps stabilize the telomerase complex.

In most types of cells, telomerase is either undetectable or active at very low levels. However, telomerase is highly active in cells that divide rapidly, such as cells that line the lungs and gastrointestinal tract, cells in bone marrow, and cells of the developing fetus. Telomerase allows these cells to divide many times without becoming damaged or undergoing apoptosis. Telomerase is also abnormally active in most cancer cells, which grow and divide without control or order.

Dyskerin is also involved in the production of ribosomal RNA (rRNA), a chemical cousin of DNA. Ribosomal RNA is required for assembling protein building blocks (amino acids) into functioning proteins.

Health Conditions Related to Genetic Changes

Dyskeratosis congenita

More than 40 mutations in the DKC1 gene have been identified in people with dyskeratosis congenita. This disorder is characterized by changes in skin coloring (pigmentation), white patches inside the mouth (oral leukoplakia), and abnormally formed fingernails and toenails (nail dystrophy). People with dyskeratosis congenita have an increased risk of developing several life-threatening conditions, including cancer and a progressive lung disease called pulmonary fibrosis. Many affected individuals also develop a serious condition called aplastic anemia, also known as bone marrow failure, which occurs when the bone marrow does not produce enough new blood cells.

Most of the DKC1 gene mutations that cause dyskeratosis congenita change single amino acids in the dyskerin protein. Researchers believe that these changes probably interfere with the dyskerin protein's ability to bind to hTR, resulting in dysfunction of the telomerase complex.

Impaired telomerase function prevents the normal maintenance of telomeres and leads to reduced telomere length. Cells that divide rapidly are especially vulnerable to the effects of shortened telomeres. As a result, people with dyskeratosis congenita may experience a variety of problems affecting quickly dividing cells in the body, such as cells of the nail beds, hair follicles, skin, lining of the mouth (oral mucosa), and bone marrow.

Breakage and instability of chromosomes resulting from inadequate telomere maintenance may lead to genetic changes that allow cells to divide in an uncontrolled way, resulting in the development of cancer in some people with dyskeratosis congenita.

More About This Health Condition

Idiopathic pulmonary fibrosis

MedlinePlus Genetics provides information about Idiopathic pulmonary fibrosis

More About This Health Condition

Other Names for This Gene

  • CBF5
  • CBF5 homolog
  • cbf5p homolog
  • DKC
  • DKC1_HUMAN
  • dyskeratosis congenita 1, dyskerin
  • dyskerin
  • FLJ97620
  • H/ACA ribonucleoprotein complex subunit 4
  • H/ACA ribonucleoprotein complex subunit 4 isoform 1
  • H/ACA ribonucleoprotein complex subunit 4 isoform 2
  • NAP57
  • NOLA4
  • nopp140-associated protein of 57 kDa
  • nucleolar protein family A member 4
  • nucleolar protein NAP57
  • snoRNP protein DKC1
  • XAP101

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Catalog of Genes and Diseases from OMIM

Research Resources

References

  • Ballew BJ, Savage SA. Updates on the biology and management of dyskeratosis congenita and related telomere biology disorders. Expert Rev Hematol. 2013 Jun;6(3):327-37. doi: 10.1586/ehm.13.23. Review. Citation on PubMed
  • Dokal I. Dyskeratosis congenita. Hematology Am Soc Hematol Educ Program. 2011;2011:480-6. doi: 10.1182/asheducation-2011.1.480. Review. Citation on PubMed
  • Gu B, Bessler M, Mason PJ. Dyskerin, telomerase and the DNA damage response. Cell Cycle. 2009 Jan 1;8(1):6-10. Epub 2009 Jan 24. Review. Citation on PubMed
  • Kirwan M, Dokal I. Dyskeratosis congenita, stem cells and telomeres. Biochim Biophys Acta. 2009 Apr;1792(4):371-9. doi: 10.1016/j.bbadis.2009.01.010. Epub 2009 Feb 7. Review. Citation on PubMed or Free article on PubMed Central
  • Kirwan M, Dokal I. Dyskeratosis congenita: a genetic disorder of many faces. Clin Genet. 2008 Feb;73(2):103-12. Epub 2007 Nov 14. Review. Citation on PubMed
  • Montanaro L. Dyskerin and cancer: more than telomerase. The defect in mRNA translation helps in explaining how a proliferative defect leads to cancer. J Pathol. 2010 Dec;222(4):345-9. doi: 10.1002/path.2777. Citation on PubMed
  • Nishio N, Kojima S. Recent progress in dyskeratosis congenita. Int J Hematol. 2010 Oct;92(3):419-24. doi: 10.1007/s12185-010-0695-5. Epub 2010 Oct 1. Review. Citation on PubMed
  • Rostamiani K, Klauck SM, Heiss N, Poustka A, Khaleghi M, Rosales R, Metzenberg AB. Novel mutations of the DKC1 gene in individuals affected with dyskeratosis congenita. Blood Cells Mol Dis. 2010 Mar-Apr;44(2):88. doi: 10.1016/j.bcmd.2009.10.005. Epub 2009 Oct 29. Citation on PubMed
  • Vulliamy TJ, Dokal I. Dyskeratosis congenita: the diverse clinical presentation of mutations in the telomerase complex. Biochimie. 2008 Jan;90(1):122-30. Epub 2007 Jul 31. Review. Citation on PubMed
  • Walne AJ, Dokal I. Advances in the understanding of dyskeratosis congenita. Br J Haematol. 2009 Apr;145(2):164-72. doi: 10.1111/j.1365-2141.2009.07598.x. Epub 2009 Feb 4. Review. Citation on PubMed or Free article on PubMed Central
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