Barbour Leslie, Xiao Wei
Department of Microbiology and Immunology, University of Saskatchewan, 107 Wiggins Road, Saskatoon, Saskatchewan S7N 5E5, Canada.
Mutat Res. 2003 Nov 27;532(1-2):137-55. doi: 10.1016/j.mrfmmm.2003.08.014.
Replication-blocking lesions result in increased genomic instability by stalling replication forks. Eukaryotic cells appear to have evolved several surveillance and repair/bypass mechanisms to ensure that replication can be resumed at these stalled forks. In the yeast Saccharomyces cerevisiae, the helicases Srs2 and Sgs1 appear to play a role in controlling the processing and stabilization of stalled replication forks. These proteins appear to be tightly regulated throughout the cell cycle and play a direct role in DNA-damage checkpoints. This allows the cells to determine the best mechanism to reestablish replication at the stalled fork: by shuttling the lesion into the RAD6-dependent pathway that can lead to error-free or error-prone bypass; or by using homologous recombination. Under conditions where both the RAD6-dependent pathway and recombination are disabled, the cells can bypass the lesion using a novel damage avoidance mechanism that is controlled by Mgs1. Replication fork bypass processes appear to be highly conserved within eukaryotes, with homologs for SGS1 and MGS1 found in both Schizosaccharomyces pombe and mammalian cells.
复制阻碍性损伤通过使复制叉停滞导致基因组不稳定性增加。真核细胞似乎已经进化出多种监测和修复/绕过机制，以确保在这些停滞的复制叉处能够重新开始复制。在酿酒酵母中，解旋酶Srs2和Sgs1似乎在控制停滞复制叉的处理和稳定方面发挥作用。这些蛋白质在整个细胞周期中似乎受到严格调控，并在DNA损伤检查点中发挥直接作用。这使细胞能够确定在停滞的复制叉处重新建立复制的最佳机制：通过将损伤转运到依赖RAD6的途径，该途径可导致无错误或易出错的绕过；或通过使用同源重组。在RAD6依赖途径和重组均被禁用的条件下，细胞可以使用由Mgs1控制的新型损伤避免机制绕过损伤。复制叉绕过过程在真核生物中似乎高度保守，在粟酒裂殖酵母和哺乳动物细胞中都发现了SGS1和MGS1的同源物。
