Department of Molecular Microbiology and Biotechnology, Tel Aviv University, Ramat Aviv 69978, Israel.
Nat Cell Biol. 2013 Jun;15(6):694-9. doi: 10.1038/ncb2745. Epub 2013 May 5.
The most dangerous insults to the genome's integrity are those that break both strands of the DNA. Double-strand breaks can be repaired by homologous recombination; in this conserved mechanism, a global genomic homology search finds sequences similar to those near the break, and uses them as a template for DNA synthesis and ligation. Chromosomes occupy restricted territories within the nucleus. We show that yeast genomic regions whose nuclear territories overlap recombine more efficiently than sequences located in spatially distant territories. Tethering of telomeres and centromeres reduces the efficiency of recombination between distant genomic loci, lowering the chances of non-allelic recombination. Our results challenge present models that posit an active scanning of the whole nuclear volume by the broken chromosomal end; they demonstrate that the search for homology is a limiting step in homologous recombination, and emphasize the importance of nuclear organization in genome maintenance.
对基因组完整性最危险的威胁是那些同时破坏 DNA 双链的因素。双链断裂可以通过同源重组来修复;在这个保守的机制中,一个全局基因组同源搜索会找到与断裂附近相似的序列,并将其用作 DNA 合成和连接的模板。染色体在核内占据受限的领土。我们表明,核区重叠的酵母基因组区域比位于空间上遥远的区域的序列更有效地进行重组。端粒和着丝粒的连接降低了远距离基因组位点之间非等位重组的效率,降低了非等位重组的可能性。我们的结果挑战了目前的模型,该模型假设断裂染色体末端主动扫描整个核体积;它们表明同源搜索是同源重组的限制步骤,并强调了核组织在基因组维护中的重要性。
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