Inbar O, Kupiec M
Department of Molecular Microbiology and Biotechnology, Tel Aviv University, Ramat Aviv 69978, Israel.
Mol Cell Biol. 1999 Jun;19(6):4134-42. doi: 10.1128/MCB.19.6.4134.
Homologous recombination is an important DNA repair mechanism in vegetative cells. During the repair of double-strand breaks, genetic information is transferred between the interacting DNA sequences (gene conversion). This event is often accompanied by a reciprocal exchange between the homologous molecules, resulting in crossing over. The repair of DNA damage by homologous recombination with repeated sequences dispersed throughout the genome might result in chromosomal aberrations or in the inactivation of genes. It is therefore important to understand how the suitable homologous partner for recombination is chosen. We have developed a system in the yeast Saccharomyces cerevisiae that can monitor the fate of a chromosomal double-strand break without the need to select for recombinants. The broken chromosome is efficiently repaired by recombination with one of two potential partners located elsewhere in the genome. One of the partners has homology to the broken ends of the chromosome, whereas the other is homologous to sequences distant from the break. Surprisingly, a large proportion of the repair is carried out by recombination involving the sequences distant from the broken ends. This repair is very efficient, despite the fact that it requires the processing of a large chromosomal region flanking the break. Our results imply that the homology search involves extensive regions of the broken chromosome and is not carried out exclusively by sequences adjacent to the double-strand break. We show that the mechanism that governs the choice of homologous partners is affected by the length and sequence divergence of the interacting partners, as well as by mutations in the mismatch repair genes. We present a model to explain how the suitable homologous partner is chosen during recombinational repair. The model provides a mechanism that may guard the integrity of the genome by preventing recombination between dispersed repeated sequences.
同源重组是营养细胞中一种重要的DNA修复机制。在双链断裂修复过程中，遗传信息在相互作用的DNA序列之间转移（基因转换）。这一事件通常伴随着同源分子之间的相互交换，从而导致交叉互换。通过与分散在整个基因组中的重复序列进行同源重组来修复DNA损伤，可能会导致染色体畸变或基因失活。因此，了解如何选择合适的同源重组伴侣非常重要。我们在酿酒酵母中开发了一个系统，该系统可以监测染色体双链断裂的修复命运，而无需选择重组体。断裂的染色体通过与位于基因组其他位置的两个潜在伴侣之一进行重组而得到有效修复。其中一个伴侣与染色体的断裂末端具有同源性，而另一个则与远离断裂处的序列同源。令人惊讶的是，很大一部分修复是通过涉及远离断裂末端的序列的重组来进行的。尽管这种修复需要处理断裂处两侧的大片染色体区域，但它非常有效。我们的结果表明，同源性搜索涉及断裂染色体的广泛区域，并非仅由双链断裂附近的序列进行。我们发现，控制同源重组伴侣选择的机制受到相互作用伴侣的长度和序列差异以及错配修复基因中的突变的影响。我们提出了一个模型来解释在重组修复过程中如何选择合适的同源重组伴侣。该模型提供了一种机制，可能通过防止分散的重复序列之间的重组来保护基因组的完整性。
