Dempsey L A, Sun H, Hanakahi L A, Maizels N
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520-8114, USA.
J Biol Chem. 1999 Jan 8;274(2):1066-71. doi: 10.1074/jbc.274.2.1066.
The immunoglobulin heavy chain switch regions contain multiple runs of guanines on the top (nontemplate) DNA strand. Here we show that LR1, a B cell-specific, duplex DNA binding factor, binds tightly and specifically to synthetic oligonucleotides containing G-G base pairs (KD </= 0.25 nM). LR1 also binds to single-stranded G-rich sequences (KD approximately 10 nM). The two subunits of LR1, nucleolin and hnRNP D, bind with high affinity to G4 DNA (KD = 0.4 and 0.5 nM, respectively). LR1 therefore contains two independent G4 DNA binding domains. We propose that LR1 binds with G-G-paired structures that form during the transcription of the S regions that is prerequisite to recombination in vivo. Interactions of donor and acceptor S regions with subunits of the LR1 could then juxtapose the switch regions for recombination.
免疫球蛋白重链转换区在顶部（非模板）DNA链上含有多个鸟嘌呤重复序列。我们在此表明，LR1是一种B细胞特异性双链DNA结合因子，它能紧密且特异地结合含有G-G碱基对的合成寡核苷酸（解离常数KD≤0.25 nM）。LR1也能结合富含鸟嘌呤的单链序列（KD约为10 nM）。LR1的两个亚基，即核仁素和不均一核糖核蛋白D，与G4 DNA具有高亲和力（解离常数KD分别为0.4和0.5 nM）。因此，LR1含有两个独立的G4 DNA结合结构域。我们提出，LR1与在S区转录过程中形成的G-G配对结构结合，这是体内重组的先决条件。然后，供体和受体S区与LR1亚基的相互作用可使转换区并列以进行重组。
