Andrews Catherine A, Clarke Duncan J
Department of Genetics, Cell Biology & Development, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
Cell Cycle. 2005 Aug;4(8):1073-7. Epub 2005 Aug 19.
The intra-S-phase checkpoint is a signaling pathway that induces slow DNA replication in the presence of DNA damage. In humans, defects in this checkpoint pathway might account for phenotypes seen in autosomal recessive diseases including ataxia telangiectasia-like disorder and Nijmegen breakage syndrome, where MRN complex components,Mre11 and Nbs1, are mutated. Here we provide evidence that the equivalent budding yeast complex, MRX (Mre11/Rad50/Xrs2), is not required for the intra-S-phase checkpoint in response to DNA alkylation damage, but is required in the presence of double-stranded DNA breaks. These data indicate, at least in budding yeast, that alternate pathways enforce replication slowing depending on the particular DNA lesion.
S期内检查点是一种信号通路，在DNA损伤存在时诱导DNA缓慢复制。在人类中，该检查点通路的缺陷可能解释了常染色体隐性疾病中出现的表型，包括共济失调毛细血管扩张样障碍和尼曼匹克氏症候群，其中MRN复合物成分Mre11和Nbs1发生了突变。在这里，我们提供证据表明，在响应DNA烷基化损伤时，S期内检查点并不需要酵母中的等效复合物MRX（Mre11/Rad50/Xrs），但在双链DNA断裂存在时则需要。这些数据表明，至少在芽殖酵母中，根据特定的DNA损伤，替代途径会促使复制减慢。
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