Department of Genetics & Development, Columbia University Medical Center, New York, New York 10032, USA.
Nat Cell Biol. 2012 Apr 8;14(5):510-7. doi: 10.1038/ncb2472.
Homologous recombination, an essential process for preserving genomic integrity, uses intact homologous sequences to repair broken chromosomes. To explore the mechanism of homologous pairing in vivo, we tagged two homologous loci in diploid yeast Saccharomyces cerevisiae cells and investigated their dynamic organization in the absence and presence of DNA damage. When neither locus is damaged, homologous loci occupy largely separate regions, exploring only 2.7% of the nuclear volume. Following the induction of a double-strand break, homologous loci co-localize ten times more often. The mobility of the cut chromosome markedly increases, allowing it to explore a nuclear volume that is more than ten times larger. Interestingly, the mobility of uncut chromosomes also increases, allowing them to explore a four times larger volume. We propose a model for homology search in which increased chromosome mobility facilitates homologous pairing. Finally, we find that the increase in DNA dynamics is dependent on early steps of homologous recombination.
同源重组是一种维持基因组完整性的重要过程，它利用完整的同源序列来修复断裂的染色体。为了研究体内同源配对的机制，我们在二倍体酵母酿酒酵母细胞中标记了两个同源基因座，并在没有和存在 DNA 损伤的情况下研究了它们的动态组织。当两个基因座都没有受损时，同源基因座占据了很大的分离区域，只探索了核体积的 2.7%。在诱导双链断裂后，同源基因座的共定位频率增加了十倍。切割染色体的流动性显著增加，使其能够探索超过核体积 10 倍的区域。有趣的是，未切割染色体的流动性也增加了，使其能够探索四倍大的体积。我们提出了一个同源搜索模型，其中增加的染色体流动性促进了同源配对。最后，我们发现 DNA 动力学的增加依赖于同源重组的早期步骤。
