RECQL4

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Species	Human	Mouse
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ATP-dependent DNA helicase Q4 is an enzyme that in humans is encoded by the RECQL4 gene.

Mutations in RECQL4 are associated with the autosomal recessive disease Rothmund-Thomson Syndrome, a disorder that has features of premature aging. In addition to the Rothmund-Thomson syndrome, RECQL4 mutations are also associated with RAPADILINO and Baller-Gerold syndromes. There are two types of Rothmund Thomson syndrome and it is Type 2 that occurs in patients carrying deleterious mutations in both copies of the RECQL4 gene. This condition is associated with a high risk of developing osteosarcoma (malignant tumor of the bone). RECQL4 gets its name from being homologous (sharing sequence) with other members of the RecQ helicase family. Two other genetic diseases are due to mutations in other RECQ helicases. Bloom syndrome is associated with mutations in the BLM gene and Werner syndrome is associated with mutations in the WRN gene.

DNA repair

Double-strand breaks in DNA are potentially lethal to a cell and need to be repaired. Repair of double-strand breaks by homologous recombination (HR) is an important cellular mechanism for avoiding this lethality. RECQL4 has a crucial role in the first step of HR, referred to as end resection. When RECQL4 is deficient, end resection, and thus HR, is reduced. Evidence suggests that other forms of DNA repair including non-homologous end joining, nucleotide excision repair and base excision repair also depend on RECQL4 function. In the Rothmund-Thomson syndrome, the association of deficient RECQL4-mediated DNA repair and premature aging is consistent with the DNA damage theory of aging.

Further reading

• Kellermayer R (2006). "The versatile RECQL4". Genet. Med. 8 (4): 213–6. doi:10.1097/01.gim.0000214457.58378.1a. PMID 16617241.
• Soukup T (1976). "Intrafusal fibre types in rat limb muscle spindles: morphological and histochemical characteristics". Histochemistry. 47 (1): 43–57. doi:10.1007/BF00492992. PMID 133085.
• Kitao S, Shimamoto A, Goto M, et al. (1999). "Mutations in RECQL4 cause a subset of cases of Rothmund-Thomson syndrome". Nat. Genet. 22 (1): 82–4. doi:10.1038/8788. PMID 10319867.
• Yankiwski V, Marciniak RA, Guarente L, Neff NF (2000). "Nuclear structure in normal and Bloom syndrome cells". Proc. Natl. Acad. Sci. U.S.A. 97 (10): 5214–9. doi:10.1073/pnas.090525897. PMC 25808. PMID 10779560.
• Kawabe T, Tsuyama N, Kitao S, et al. (2000). "Differential regulation of human RecQ family helicases in cell transformation and cell cycle". Oncogene. 19 (41): 4764–72. doi:10.1038/sj.onc.1203841. PMID 11032027.
• Wang LL, Worley K, Gannavarapu A, et al. (2002). "Intron-size constraint as a mutational mechanism in Rothmund-Thomson syndrome". Am. J. Hum. Genet. 71 (1): 165–7. doi:10.1086/341234. PMC 384974. PMID 12016592.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Roversi G, Beghini A, Zambruno G, et al. (2003). "Identification of two novel RECQL4exonic SNPs and genomic characterization of the IVS12 minisatellite". J. Hum. Genet. 48 (2): 107–9. doi:10.1007/s100380300016. PMID 12601557.
• Wang LL, Gannavarapu A, Clericuzio CL, et al. (2004). "Absence of RECQL4 mutations in poikiloderma with neutropenia in Navajo and non-Navajo patients". Am. J. Med. Genet. A. 118 (3): 299–301. doi:10.1002/ajmg.a.10057. PMID 12673665.
• Beghini A, Castorina P, Roversi G, et al. (2004). "RNA processing defects of the helicase gene RECQL4 in a compound heterozygous Rothmund-Thomson patient". Am. J. Med. Genet. A. 120 (3): 395–9. doi:10.1002/ajmg.a.20154. PMID 12838562.
• Siitonen HA, Kopra O, Kääriäinen H, et al. (2004). "Molecular defect of RAPADILINO syndrome expands the phenotype spectrum of RECQL diseases". Hum. Mol. Genet. 12 (21): 2837–44. doi:10.1093/hmg/ddg306. PMID 12952869.
• Brandenberger R, Wei H, Zhang S, et al. (2005). "Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation". Nat. Biotechnol. 22 (6): 707–16. doi:10.1038/nbt971. PMID 15146197.
• Nishijo K, Nakayama T, Aoyama T, et al. (2004). "Mutation analysis of the RECQL4 gene in sporadic osteosarcomas". Int. J. Cancer. 111 (3): 367–72. doi:10.1002/ijc.20269. PMID 15221963.
• Yin J, Kwon YT, Varshavsky A, Wang W (2005). "RECQL4, mutated in the Rothmund-Thomson and RAPADILINO syndromes, interacts with ubiquitin ligases UBR1 and UBR2 of the N-end rule pathway". Hum. Mol. Genet. 13 (20): 2421–30. doi:10.1093/hmg/ddh269. PMID 15317757.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
• Sengupta S, Shimamoto A, Koshiji M, et al. (2005). "Tumor suppressor p53 represses transcription of RECQ4 helicase". Oncogene. 24 (10): 1738–48. doi:10.1038/sj.onc.1208380. PMID 15674334.

External links

• GeneReviews/NCBI/NIH/UW entry on Rothmund-Thomson Syndrome