| H00296 | |
| H number | H00296 |
| Name | Defects in RecQ helicases |
| Description | RecQ helicases have crucial roles in the maintenance of genome stability. In humans, it is known that deficiencies in three of the five human RecQ helicases cause genetic disorders characterized by cancer predisposition, premature aging and developmental abnormalities. These disorders are Bloom's syndrome (BS), Werner's syndrome (WS), and Rothmund-Thomson syndrome (RTS), which are caused by mutations in BLM, WRN and RECQL4, respectively. Despite the apparent structural and biochemical similarities between the BLM, WRN and RECQL4 proteins, the phenotypes of BS, WS and RTS are different, suggesting that each disease pathway is functionally distinct to some extent. BS is characterized by most prominently, a predisposition to all types of cancers. WS is characterized by the premature development of features that resemble aging. RTS is characterized by skin and skeletal abnormalities, signs of premature aging, and cancer predisposition, especially to osteosarcomas. Recent research has shown many connections between all three proteins and the regulation of excess HR (Homologous recombination). It was also indicated that BLM is involved in repair of stalled DNA replication forks, and that WRN is required for telomere maintenance. Mutations in RECQL4 also associate with 2 additional syndromes, Rapadilino and Baller-Gerold syndrome. |
| Category | Congenital malformation |
| Network | - |
| Gene | BLM [HSA:641] [KO:K10901] WRN [HSA:7486] [KO:K10900] RECQL4 [HSA:9401] [KO:K10730] |
| Pathogen | - |
| Env factor | - |
| Carcinogen | - |
| Drug | - |
| Comment | Disorder of DNA repair system |
| Other DBs | ICD-10: Q82.8 MeSH: D001816 D014898 D011038 C535288 OMIM: 210900 277700 268400 266280 218600 |
| Reference | PMID:12200042 AUTHORS Mohaghegh P, Hickson ID TITLE Premature aging in RecQ helicase-deficient human syndromes. JOURNAL Int J Biochem Cell Biol 34:1496-501 (2002) DOI:10.1016/S1357-2725(02)00039-0 PMID:18430459 AUTHORS Ouyang KJ, Woo LL, Ellis NA. TITLE Homologous recombination and maintenance of genome integrity: Cancer and aging through the prism of human RecQ helicases. JOURNAL Mech Ageing Dev 129:425-40 (2008) DOI:10.1016/j.mad.2008.03.003 PMID:17571213 AUTHORS Hanada K, Hickson ID TITLE Molecular genetics of RecQ helicase disorders. JOURNAL Cell Mol Life Sci 64:2306-22 (2007) DOI:10.1007/s00018-007-7121-z PMID:19661064 AUTHORS Kikuchi K, Abdel-Aziz HI, Taniguchi Y, Yamazoe M, Takeda S, Hirota K TITLE Bloom DNA helicase facilitates homologous recombination between diverged homologous sequences. JOURNAL J Biol Chem 284:26360-7 (2009) DOI:10.1074/jbc.M109.029348 |