Pont-Kingdon G, Dawson R J, Carroll D
Department of Biochemistry, University of Utah School of Medicine, Salt Lake City 84132.
EMBO J. 1993 Jan;12(1):23-34. doi: 10.1002/j.1460-2075.1993.tb05628.x.
Several molecular mechanisms have been proposed to account for nonconservative homologous recombination. This type of recombination is particularly efficient in Xenopus oocytes when appropriate DNA substrates are injected. To distinguish between possible models, we have investigated recombination intermediates from oocytes by direct observation in the electron microscope. Partially recombined DNA was crosslinked with a psoralen derivative after incubation in oocytes to limit the branch migration that might occur during recovery procedures and alter the structures that were initially present. Branched structures, which we interpret as intermediates, represented approximately 10% of the DNA recovered and were readily analyzed. We did not observe any structures with internal loops predicted by invasion mechanisms. The majority of intermediates had one or two single-stranded branches on product-sized molecules, as predicted for incomplete junctions in the resection-annealing mechanism. Detailed length measurements confirmed the expectations of that model. When recovered DNA was not crosslinked, or when annealed junctions were prepared in vitro, we saw branched structures that indicated the occurrence of extensive branch migration. Comparison with the crosslinked sample confirmed the effectiveness of the crosslinking in preserving structures created in the oocytes. Our results strongly support a resection-annealing mechanism of recombination in oocytes.
已经提出了几种分子机制来解释非保守同源重组。当注射合适的DNA底物时,这种重组类型在非洲爪蟾卵母细胞中特别有效。为了区分可能的模型,我们通过电子显微镜直接观察研究了来自卵母细胞的重组中间体。在卵母细胞中孵育后,部分重组的DNA与补骨脂素衍生物交联,以限制在回收过程中可能发生的分支迁移,并改变最初存在的结构。我们将其解释为中间体的分支结构约占回收DNA的10%,并且易于分析。我们没有观察到任何由侵入机制预测的具有内部环的结构。正如切除退火机制中不完全连接所预测的那样,大多数中间体在产物大小的分子上有一个或两个单链分支。详细的长度测量证实了该模型的预期。当回收的DNA未交联时,或者当在体外制备退火连接时,我们看到了表明发生广泛分支迁移的分支结构。与交联样品的比较证实了交联在保留卵母细胞中形成的结构方面的有效性。我们的结果有力地支持了卵母细胞中重组的切除退火机制。