Werner syndrome protein: biochemical properties and functional interactions.
Werner syndrome is a premature aging syndrome displaying numerous signs and symptoms found in normal aging. The disease is associated with a mutation in the WRN gene. We have purified the Werner protein (WRN) and studied its biochemical activities and its protein interactions. WRN is a helicase and an exonuclease and also has an associated ATPase activity. WRN interacts physically and functionally with replication protein A (RPA), which stimulates its helicase activity. We have studied the WRN exonuclease activity and found that it can be blocked by certain DNA lesions and not by others. Thus, while WRN does not bind to DNA damage, it may have properties that allow it to sense the presence of damage in DNA. More recently we have found other protein interactions that involve physical and functional interactions with WRN, which could suggest a role for WRN in DNA repair.
Bohr
V A
VA
Laboratory of Molecular Genetics, National Institute on Aging, NIH, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA. vbohr@nih.gov
Cooper
M
M
Orren
D
D
Machwe
A
A
Piotrowski
J
J
Sommers
J
J
Karmakar
P
P
Brosh
R
R
D034961:Antigens, Nuclear; D004249:DNA Damage; D004265:DNA Helicases / Q000235:genetics / Q000502:physiology*; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000502:physiology; D005090:Exodeoxyribonucleases; D006801:Humans; D000072200:Ku Autoantigen; D009687:Nuclear Proteins / Q000502:physiology; D053484:RecQ Helicases; D014898:Werner Syndrome / Q000209:etiology* / Q000235:genetics; D000071657:Werner Syndrome Helicase
D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D005090:Exodeoxyribonucleases; D004265:DNA Helicases; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase; C106893:XRCC5 protein, human; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen