Normal Function
The DDX11 gene provides instructions for making an enzyme called ChlR1, which functions as a helicase. Helicases are enzymes that attach (bind) to DNA and temporarily unwind the two spiral strands (double helix) of the DNA molecule so it can be copied (replicated) in preparation for cell division. ChlR1 is also involved in repairing any errors that are made when DNA is copied. In addition, ChlR1 is involved in other processes leading up to cell division. After replication, the DNA from each chromosome is arranged into two identical structures, called sister chromatids, which the ChlR1 enzyme helps to keep together until they are ready to separate into individual cells. This enzyme also ensures proper separation of chromatids during cell division. By helping repair errors in DNA and ensuring proper DNA replication, the ChlR1 enzyme plays a role in maintaining the stability of a cell's genetic information.
Health Conditions Related to Genetic Changes
Warsaw breakage syndrome
At least three mutations in the DDX11 gene have been found to cause Warsaw breakage syndrome. This condition causes multiple abnormalities that may include impaired growth, distinctive facial features, hearing loss, and heart malformations. The mutations that cause Warsaw breakage syndrome severely reduce or completely eliminate ChlR1 enzyme activity. As a result, the enzyme cannot bind to DNA and cannot unwind the DNA strands to help with DNA replication and repair. A lack of functional ChlR1 impairs cell division and leads to an accumulation of DNA damage. This DNA damage can appear as breaks in the DNA, giving the condition its name. It is unclear how these problems in DNA maintenance lead to the specific abnormalities characteristic of Warsaw breakage syndrome.
More About This Health ConditionOther Names for This Gene
- CHL1-related helicase gene-1
- CHL1-related protein 1
- CHLR1
- DDX11_HUMAN
- DEAD/H (Asp-Glu-Ala-Asp/His) box helicase 11
- DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 11 (CHL1-like helicase homolog, S. cerevisiae)
- DEAD/H box protein 11
- hCHLR1
- keratinocyte growth factor-regulated gene 2 protein
- KRG-2
- KRG2
- probable ATP-dependent RNA helicase DDX11
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Capo-Chichi JM, Bharti SK, Sommers JA, Yammine T, Chouery E, Patry L, Rouleau GA, Samuels ME, Hamdan FF, Michaud JL, Brosh RM Jr, Megarbane A, Kibar Z. Identification and biochemical characterization of a novel mutation in DDX11 causing Warsaw breakage syndrome. Hum Mutat. 2013 Jan;34(1):103-7. doi: 10.1002/humu.22226. Epub 2012 Oct 17. Citation on PubMed or Free article on PubMed Central
- Inoue A, Hyle J, Lechner MS, Lahti JM. Mammalian ChlR1 has a role in heterochromatin organization. Exp Cell Res. 2011 Oct 15;317(17):2522-35. doi: 10.1016/j.yexcr.2011.08.006. Epub 2011 Aug 11. Citation on PubMed or Free article on PubMed Central
- Shah N, Inoue A, Woo Lee S, Beishline K, Lahti JM, Noguchi E. Roles of ChlR1 DNA helicase in replication recovery from DNA damage. Exp Cell Res. 2013 Aug 15;319(14):2244-53. doi: 10.1016/j.yexcr.2013.06.005. Epub 2013 Jun 22. Citation on PubMed or Free article on PubMed Central
- van der Lelij P, Chrzanowska KH, Godthelp BC, Rooimans MA, Oostra AB, Stumm M, Zdzienicka MZ, Joenje H, de Winter JP. Warsaw breakage syndrome, a cohesinopathy associated with mutations in the XPD helicase family member DDX11/ChlR1. Am J Hum Genet. 2010 Feb 12;86(2):262-6. doi: 10.1016/j.ajhg.2010.01.008. Epub 2010 Feb 4. Citation on PubMed or Free article on PubMed Central
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