KEGG   DISEASE: Defects in RecQ helicasesHelp
H00296                      Disease                                

Defects in RecQ helicases, including:
Bloom's syndrome [DS:H01346];
Werner's syndrome [DS:H01733];
Rothmund-Thomson syndrome [DS:H01734];
RAPADILINO syndrome [DS:H00965];
Baller-Gerold syndrome
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 RECQ4, respectively. Despite the apparent structural and biochemical similarities between the BLM, WRN and RECQ4 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.
Congenital disorder of DNA repair systems
Human diseases [BR:br08402]
 Congenital disorders of metabolism
  Congenital disorders of DNA repair systems
   H00296  Defects in RecQ helicases
Human diseases in ICD-10 classification [BR:br08403]
 4. Endocrine, nutritional and metabolic diseases (E00-E90)
  E20-E35  Disorders of other endocrine glands
   E34  Other endocrine disorders
    H00296  Defects in RecQ helicases
 17. Congenital malformations, deformations and chromosomal abnormalities (Q00-Q99)
  Q80-Q89  Other congenital malformations
   Q82  Other congenital malformations of skin
    H00296  Defects in RecQ helicases
BRITE hierarchy
Homologous recombination
BLM [HSA:641] [KO:K10901]
WRN [HSA:7486] [KO:K10900]
RECQL4 [HSA:9401] [KO:K10730]
DNA replication proteins [BR:ko03032]
DNA repair and recombination proteins [BR:ko03400]
Other DBs
Mohaghegh P, Hickson ID
Premature aging in RecQ helicase-deficient human syndromes.
Int J Biochem Cell Biol 34:1496-501 (2002)
Ouyang KJ, Woo LL, Ellis NA.
Homologous recombination and maintenance of genome integrity: Cancer and aging through the prism of human RecQ helicases.
Mech Ageing Dev 129:425-40 (2008)
Hanada K, Hickson ID
Molecular genetics of RecQ helicase disorders.
Cell Mol Life Sci 64:2306-22 (2007)
Kikuchi K, Abdel-Aziz HI, Taniguchi Y, Yamazoe M, Takeda S, Hirota K
Bloom DNA helicase facilitates homologous recombination between diverged homologous sequences.
J Biol Chem 284:26360-7 (2009)

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