Sun H, Karow J K, Hickson I D, Maizels N
Departments of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520-8114, USA.
J Biol Chem. 1998 Oct 16;273(42):27587-92. doi: 10.1074/jbc.273.42.27587.
BLM, the gene that is defective in Bloom's syndrome, encodes a protein homologous to RecQ subfamily helicases that functions as a 3'-5' DNA helicase in vitro. We now report that the BLM helicase can unwind G4 DNA. The BLM G4 DNA unwinding activity is ATP-dependent and requires a short 3' region of single-stranded DNA. Strikingly, G4 DNA is a preferred substrate of the BLM helicase, as measured both by efficiency of unwinding and by competition. These results suggest that G4 DNA may be a natural substrate of BLM in vivo and that the failure to unwind G4 DNA may cause the genomic instability and increased frequency of sister chromatid exchange characteristic of Bloom's syndrome.
BLM基因在布卢姆综合征中存在缺陷,它编码一种与RecQ亚家族解旋酶同源的蛋白质,该蛋白质在体外作为3'-5' DNA解旋酶发挥作用。我们现在报告称,BLM解旋酶能够解开G4 DNA。BLM的G4 DNA解旋活性依赖于ATP,并且需要一段短的3'单链DNA区域。引人注目的是,无论是通过解旋效率还是竞争实验来衡量,G4 DNA都是BLM解旋酶的优选底物。这些结果表明,G4 DNA可能是BLM在体内的天然底物,而无法解开G4 DNA可能会导致基因组不稳定以及布卢姆综合征所特有的姐妹染色单体交换频率增加。