Milot E, Belmaaza A, Wallenburg J C, Gusew N, Bradley W E, Chartrand P
Canadian Red Cross Society, Research and Development, Montréal Centre, Sherbrooke, Québec, Canada.
EMBO J. 1992 Dec;11(13):5063-70. doi: 10.1002/j.1460-2075.1992.tb05613.x.
Illegitimate recombination is the most frequent mechanism for chromosomal rearrangements in mammalian cells, yet little is known about this process. Most of the studies to date have looked at the sequences present at illegitimate junctions. These revealed the presence of recurrent DNA motifs, none of which was consistently found. We have undertaken to determine if intrinsic DNA structures such as bent DNA elements could be a major determinant in chromosomal illegitimate recombination. Using a two dimensional electrophoretic assay we found that eight out of eight junctions, resulting from various types of chromosomal rearrangements, had migration behaviour characteristic of DNA containing intrinsically bent DNA elements. In all cases, these occurred within one kilobase of the junctions, and in most cases could be found in both participating DNA segments. We also found that these bent DNA elements were present before the recombination event. When we analysed the frequency of intrinsically bent DNA elements in random chromosomal fragments, we found it to be about one per 11 kilobases. Thus these results suggest that bent DNA is associated with chromosomal illegitimate recombination.
非法重组是哺乳动物细胞中染色体重排最常见的机制,但人们对这一过程知之甚少。迄今为止,大多数研究都着眼于非法连接点处存在的序列。这些研究揭示了反复出现的DNA基序的存在,但没有一个是始终能被发现的。我们已着手确定诸如弯曲DNA元件等内在DNA结构是否可能是染色体内非法重组的主要决定因素。使用二维电泳分析,我们发现,由各种类型的染色体重排产生的八个连接点中的八个,具有含内在弯曲DNA元件的DNA的迁移行为特征。在所有情况下,这些都出现在连接点的一千碱基范围内,并且在大多数情况下,在两个参与的DNA片段中都能找到。我们还发现,这些弯曲DNA元件在重组事件之前就已存在。当我们分析随机染色体片段中内在弯曲DNA元件的频率时,我们发现其约为每11千碱基一个。因此,这些结果表明弯曲DNA与染色体内非法重组有关。