Two modes of DNA double-strand break repair are reciprocally regulated through the fission yeast cell cycle
Two modes of DNA double-strand break repair are reciprocally regulated through the fission yeast cell cycle
复制标题
DOI：
10.1101/gad.315804
复制
发表时间：
2004-09-15
影响因子：
10.5
通讯作者：
Cooper, JP
中科院分区：
文献类型：
--
作者：
Ferreira, MG;Cooper, JP
一些考虑表明，双链断裂（DSB）修复的两种主要模式，同源重组（HR）和非同源末端连接（NHEJ）的水平，通过细胞周期进行调节。然而，这个想法还没有得到明确的测试。在没有端粒结合蛋白Taz 1的情况下，裂殖酵母通过NHEJ进行致命的端粒融合。这些融合仅发生在氮饥饿期间，并且在对数生长期间不能积累，此时大多数细胞处于G2。我们表明，G1期阻滞是特定的氮饥饿诱导的事件，促进NHEJ之间的taz 1（-）端粒。此外，NHEJ和HR的一般水平通过细胞周期进行调节，因此NHEJ在G1早期比其他细胞周期阶段高10倍;相反的是HR. While NHEJ是已知的DSB在循环细胞中的存活率，我们发现它是G1期间产生的DSB的修复和存活的关键。
Several considerations suggest that levels of the two major modes of double-strand break (DSB) repair, homologous recombination (HR), and nonhomologous end joining (NHEJ), are regulated through the cell cycle. However, this idea has not been explicitly tested. In the absence of the telomere-binding protein Taz1, fission yeast undergo lethal telomere fusions via NHEJ. These fusions occur only during periods of nitrogen starvation and fail to accumulate during logarithmic growth, when the majority of cells are in G2. We show that G1 arrest is the specific nitrogen starvation-induced event that promotes NHEJ between taz1(-) telomeres. Furthermore, the general levels of NHEJ and HR are reciprocally regulated through the cell cycle, so that NHEJ is 10-fold higher in early G1 than in other cell cycle stages; the reverse is true for HR. Whereas NHEJ is known to be dispensable for survival of DSBs in cycling cells, we find that it is critical for repair and survival of DSBs arising during G1.