Biology:Dyskerin
 Generic protein structure example |
H/ACA ribonucleoprotein complex subunit 4 is a protein that in humans is encoded by the gene DKC1.[1][2][3]
Dyskerin is a pseudouridine synthase enzyme which is part of the TruB family of enzymes.[4] Dyskerin is an L-shaped protein of 514 residues and a molecular weight of about 58 kilo-daltons.[4] Dyskerin is essential for the activity of telomerase by accumulating Telomerase RNA Component (TERC).[4]
This gene is a member of the H/ACA snoRNPs (small nucleolar ribonucleoproteins) gene family. snoRNPs are involved in various aspects of rRNA processing and modification and have been classified into two families: C/D and H/ACA. The H/ACA snoRNPs also include the NOLA1, 2 and 3 proteins. The protein encoded by this gene and the three NOLA proteins localize to the dense fibrillar components of nucleoli and to coiled (Cajal) bodies in the nucleus. Both 18S rRNA production and rRNA pseudouridylation are impaired if any one of the four proteins is depleted. The protein encoded by this gene is related to the Saccharomyces cerevisiae Cbf5p and Drosophila melanogaster Nop60B proteins. The gene lies in a tail-to-tail orientation with the palmitoylated erythrocyte membrane protein (MPP1) gene and is transcribed in a telomere to centromere direction. Both nucleotide substitutions and single trinucleotide repeat polymorphisms have been found in this gene. Mutations in this gene cause X-linked dyskeratosis congenita.[3]
Clinical significance
Mutations in DKC1 are associated to Hoyeraal-Hreidarsson syndrome.[5]
References
- ↑ "X-linked dyskeratosis congenita is caused by mutations in a highly conserved gene with putative nucleolar functions". Nat Genet 19 (1): 32–8. May 1998. doi:10.1038/ng0598-32. PMID 9590285.
- ↑ "Mapping and characterization of the X-linked dyskeratosis congenita (DKC) gene". Genomics 55 (1): 21–7. Mar 1999. doi:10.1006/geno.1998.5600. PMID 9888995.
- ↑ 3.0 3.1 "Entrez Gene: DKC1 dyskeratosis congenita 1, dyskerin". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1736.
- ↑ 4.0 4.1 4.2 "Dyskerin: an essential pseudouridine synthase with multifaceted roles in ribosome biogenesis, splicing, and telomere maintenance". RNA 27 (12): 1441–1458. 2021. doi:10.1261/rna.078953.121. PMID 34556550.
- ↑ Lim, B. C.; Yoo, S. K.; Lee, S; Shin, J. Y.; Hwang, H; Chae, J. H.; Hwang, Y. S.; Seo, J. S. et al. (2014). "Hoyeraal-Hreidarsson syndrome with a DKC1 mutation identified by whole-exome sequencing". Gene 546 (2): 425–9. doi:10.1016/j.gene.2014.06.011. PMID 24914498.
Further reading
- "Dyskeratosis congenita: molecular insights into telomerase function, ageing and cancer". Expert Reviews in Molecular Medicine 6 (26): 1–23. 2004. doi:10.1017/S1462399404008671. PMID 15613268.
- Yamaguchi H (2007). "Mutations of telomerase complex genes linked to bone marrow failures". Journal of Nippon Medical School 74 (3): 202–9. doi:10.1272/jnms.74.202. PMID 17625368.
- "The Hoyeraal-Hreidarsson syndrome: the fourth case of a separate entity with prenatal growth retardation, progressive pancytopenia and cerebellar hypoplasia". Eur. J. Pediatr. 154 (4): 304–8. 1995. doi:10.1007/BF01957367. PMID 7607282.
- "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene 138 (1–2): 171–4. 1994. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
- "Skewed X-chromosome inactivation in female carriers of dyskeratosis congenita". Am. J. Hum. Genet. 60 (3): 581–7. 1997. PMID 9042917.
- "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (1–2): 149–56. 1997. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
- McGrath JA (1999). "Dyskeratosis congenita: new clinical and molecular insights into ribosome function". Lancet 353 (9160): 1204–5. doi:10.1016/S0140-6736(99)00011-2. PMID 10217077.
- "X-linked dyskeratosis congenita is predominantly caused by missense mutations in the DKC1 gene". Am. J. Hum. Genet. 65 (1): 50–8. 1999. doi:10.1086/302446. PMID 10364516.
- "Dyskeratosis congenita caused by a 3' deletion: germline and somatic mosaicism in a female carrier". Blood 94 (4): 1254–60. 1999. doi:10.1182/blood.V94.4.1254. PMID 10438713.
- "Dyskerin localizes to the nucleolus and its mislocalization is unlikely to play a role in the pathogenesis of dyskeratosis congenita". Hum. Mol. Genet. 8 (13): 2515–24. 2000. doi:10.1093/hmg/8.13.2515. PMID 10556300.
- "Unexplained aplastic anaemia, immunodeficiency, and cerebellar hypoplasia (Hoyeraal-Hreidarsson syndrome) due to mutations in the dyskeratosis congenita gene, DKC1". Br. J. Haematol. 107 (2): 335–9. 2000. doi:10.1046/j.1365-2141.1999.01690.x. PMID 10583221.
- "A telomerase component is defective in the human disease dyskeratosis congenita". Nature 402 (6761): 551–5. 1999. doi:10.1038/990141. PMID 10591218. Bibcode: 1999Natur.402..551M.
- "Overlap of dyskeratosis congenita with the Hoyeraal-Hreidarsson syndrome". J. Pediatr. 136 (3): 390–3. 2000. doi:10.1067/mpd.2000.104295. PMID 10700698.
- "Gene structure and expression of the mouse dyskeratosis congenita gene, dkc1". Genomics 67 (2): 153–63. 2000. doi:10.1006/geno.2000.6227. PMID 10903840.
- "Human H/ACA Small Nucleolar RNPs and Telomerase Share Evolutionarily Conserved Proteins NHP2 and NOP10". Mol. Cell. Biol. 20 (23): 9028–40. 2000. doi:10.1128/MCB.20.23.9028-9040.2000. PMID 11074001.
- "DNA Cloning Using In Vitro Site-Specific Recombination". Genome Res. 10 (11): 1788–95. 2001. doi:10.1101/gr.143000. PMID 11076863.
- "Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing". EMBO Rep. 1 (3): 287–92. 2001. doi:10.1093/embo-reports/kvd058. PMID 11256614.
- "Identification of novel DKC1 mutations in patients with dyskeratosis congenita: implications for pathophysiology and diagnosis". Hum. Genet. 108 (4): 299–303. 2001. doi:10.1007/s004390100494. PMID 11379875.
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