Bohr V A, Cooper M, Orren D, Machwe A, Piotrowski J, Sommers J, Karmakar P, Brosh R
Laboratory of Molecular Genetics, National Institute on Aging, NIH, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA.
Exp Gerontol. 2000 Sep;35(6-7):695-702. doi: 10.1016/s0531-5565(00)00145-5.
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.
沃纳综合征是一种早衰综合征，表现出许多在正常衰老过程中出现的体征和症状。该疾病与WRN基因的突变有关。我们已经纯化了沃纳蛋白（WRN），并研究了其生化活性及其蛋白质相互作用。WRN是一种解旋酶和核酸外切酶，还具有相关的ATP酶活性。WRN在物理和功能上与复制蛋白A（RPA）相互作用，RPA可刺激其解旋酶活性。我们研究了WRN核酸外切酶活性，发现它可被某些DNA损伤阻断，而不受其他损伤的影响。因此，虽然WRN不与DNA损伤结合，但它可能具有使其能够感知DNA中损伤存在的特性。最近我们发现了其他与WRN发生物理和功能相互作用的蛋白质相互作用，这可能表明WRN在DNA修复中起作用。
