Miyabe Izumi, Mizuno Ken'Ichi, Keszthelyi Andrea, Daigaku Yasukazu, Skouteri Meliti, Mohebi Saed, Kunkel Thomas A, Murray Johanne M, Carr Antony M
Genome Damage and Stability Centre, University of Sussex, Brighton, UK.
Frontier Research Institute for Interdisciplinary Sciences, Tohoku University, Sendai, Japan.
Nat Struct Mol Biol. 2015 Nov;22(11):932-8. doi: 10.1038/nsmb.3100. Epub 2015 Oct 5.
To maintain genetic stability, DNA must be replicated only once per cell cycle, and replication must be completed even when individual replication forks are inactivated. Because fork inactivation is common, passive convergence of an adjacent fork is insufficient to rescue all inactive forks. Thus, eukaryotic cells have evolved homologous recombination-dependent mechanisms to restart persistent inactive forks. Completing DNA synthesis via homologous recombination-restarted replication (HoRReR) ensures cell survival, but at a cost. One such cost is increased mutagenesis because HoRReR is more error prone than canonical replication. This increased error rate implies the HoRReR mechanism is distinct from that of a canonical fork. Here we demonstrate, in Schizosaccharomyces pombe, that a DNA sequence duplicated by HoRReR during S phase is replicated semiconservatively, but both the leading and lagging strands are synthesized by DNA polymerase δ.
为维持遗传稳定性，DNA在每个细胞周期必须仅复制一次，并且即使单个复制叉失活，复制也必须完成。由于复制叉失活很常见，相邻复制叉的被动汇合不足以挽救所有失活的复制叉。因此，真核细胞进化出了依赖同源重组的机制来重启持续失活的复制叉。通过同源重组重启的复制（HoRReR）完成DNA合成可确保细胞存活，但要付出代价。其中一个代价是诱变增加，因为HoRReR比经典复制更容易出错。这种增加的错误率意味着HoRReR机制与经典复制叉的机制不同。在这里，我们在粟酒裂殖酵母中证明，在S期由HoRReR复制的DNA序列以半保留方式复制，但前导链和后随链均由DNA聚合酶δ合成。
