Labib Karim, Hodgson Ben
Cancer Research UK, Paterson Institute for Cancer Research, University of Manchester, Wilmslow Road, Manchester M20 4BX, UK.
EMBO Rep. 2007 Apr;8(4):346-53. doi: 10.1038/sj.embor.7400940.
Defects in chromosome replication can lead to translocations that are thought to result from recombination events at stalled DNA replication forks. The progression of forks is controlled by an essential DNA helicase, which unwinds the parental duplex and can stall on encountering tight protein-DNA complexes. Such pause sites are hotspots for recombination and it has been proposed that stalled replisomes disassemble, leading to fork collapse. However, in both prokaryotes and eukaryotes it now seems that paused forks are surprisingly stable, so that DNA synthesis can resume without recombination if the barrier protein is removed. Recombination at stalled forks might require other events that occur after pausing, or might be dependent on features of the surrounding DNA sequence. These findings have important implications for our understanding of the regulation of genome stability in eukaryotic cells, in which pausing of forks is mediated by specific proteins that are associated with the replicative helicase.
染色体复制缺陷可导致易位，这种易位被认为是由停滞的DNA复制叉处的重组事件引起的。复制叉的进展由一种必需的DNA解旋酶控制，该酶解开亲本双链，并在遇到紧密的蛋白质-DNA复合物时停滞。这些停顿位点是重组的热点，有人提出停滞的复制体解体，导致复制叉崩溃。然而，现在看来，在原核生物和真核生物中，停顿的复制叉都出奇地稳定，因此如果去除障碍蛋白，DNA合成可以在不发生重组的情况下恢复。停滞复制叉处的重组可能需要停顿后发生的其他事件，或者可能取决于周围DNA序列的特征。这些发现对于我们理解真核细胞中基因组稳定性的调控具有重要意义，在真核细胞中，复制叉的停顿由与复制解旋酶相关的特定蛋白质介导。
