Aylon Yael, Kupiec Martin
Department of Molecular Microbiology and Biotechnology, Tel Aviv University, Ramat Aviv 69978, Israel.
Mutat Res. 2004 May;566(3):231-48. doi: 10.1016/j.mrrev.2003.10.001.
Genome stability is of primary importance for the survival and proper functioning of all organisms. Double-strand breaks (DSBs) arise spontaneously during growth, or can be created by external insults. Repair of DSBs by homologous recombination provides an efficient and fruitful pathway to restore chromosomal integrity. Exciting new work in yeast has lately provided insights into this complex process. Many of the proteins involved in recombination have been isolated and the details of the repair mechanism are now being unraveled at the molecular level. In this review, we focus on recent studies which dissect the recombinational repair of a single broken chromosome. After DSB formation, a decision is made regarding the mechanism of repair (recombination or non-homologous end-joining). This decision is under genetic control. Once committed to the recombination pathway, the broken chromosomal ends are resected by a still unclear mechanism in which the DNA damage checkpoint protein Rad24 participates. At this stage several proteins are recruited to the broken ends, including Rad51p, Rad52p, Rad55p, Rad57p, and possibly Rad54p. A genomic search for homology ensues, followed by strand invasion, promoted by the Rad51 filament with the participation of Rad55p, Rad57p and Rad54p. DNA synthesis then takes place, restoring the resected ends. Crossing-over formation depends on the length of the homologous recombining sequences, and is usually counteracted by the activity of the mismatch repair system. Given the conservation of the repair mechanisms and genes throughout evolution, these studies have profound implications for other eukaryotic organisms.
基因组稳定性对于所有生物体的生存和正常功能至关重要。双链断裂（DSB）在生长过程中自发产生，或可由外部损伤导致。通过同源重组修复DSB为恢复染色体完整性提供了一条高效且富有成效的途径。酵母中令人兴奋的新研究最近为这一复杂过程提供了见解。许多参与重组的蛋白质已被分离出来，修复机制的细节目前正在分子水平上被揭示。在这篇综述中，我们聚焦于最近剖析单个断裂染色体的重组修复的研究。DSB形成后，需就修复机制（重组或非同源末端连接）做出决定。这一决定受遗传控制。一旦确定采用重组途径，断裂的染色体末端会通过一种尚不清楚的机制进行切除，DNA损伤检查点蛋白Rad24参与其中。在这个阶段，几种蛋白质会被招募到断裂末端，包括Rad51p、Rad52p、Rad55p、Rad57p，可能还有Rad54p。随后会在基因组中搜索同源性，接着在Rad51丝状体的促进下，在Rad55p、Rad57p和Rad54p的参与下发生链入侵。然后进行DNA合成，恢复切除的末端。交叉形成取决于同源重组序列的长度，并且通常会受到错配修复系统活性的抵消。鉴于修复机制和基因在整个进化过程中的保守性，这些研究对其他真核生物具有深远意义。
