KEGG   DISEASE: H00296Help
Entry
H00296                      Disease                                

Name
Defects in RecQ helicases, including:
Bloom's syndrome [DS:H01346];
Werner's syndrome;
Rothmund-Thomson syndrome;
RAPADILINO syndrome [DS:H00965]
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 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.
Category
Congenital disorder of DNA repair systems
BRITE hierarchy
Pathway
Homologous recombination
Gene
BLM; Bloom syndrome, RecQ helicase-like [HSA:641] [KO:K10901]
WRN; Werner syndrome, RecQ helicase-like [HSA:7486] [KO:K10900]
RECQL4; RecQ protein-like 4 [HSA:9401] [KO:K10730]
Comment
DNA replication proteins [BR:ko03032]
DNA repair and recombination proteins [BR:ko03400]
Other DBs
Reference
  Authors
Mohaghegh P, Hickson ID
  Title
Premature aging in RecQ helicase-deficient human syndromes.
  Journal
Int J Biochem Cell Biol 34:1496-501 (2002)
Reference
  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)
Reference
  Authors
Hanada K, Hickson ID
  Title
Molecular genetics of RecQ helicase disorders.
  Journal
Cell Mol Life Sci 64:2306-22 (2007)
Reference
  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)

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