Vincent Jack A, Kwong Tracey J, Tsukiyama Toshio
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, Washington 98109, USA.
Nat Struct Mol Biol. 2008 May;15(5):477-84. doi: 10.1038/nsmb.1419. Epub 2008 Apr 13.
The eukaryotic DNA replication machinery must traverse every nucleosome in the genome during S phase. As nucleosomes are generally inhibitory to DNA-dependent processes, chromatin structure must undergo extensive reorganization to facilitate DNA synthesis. However, the identity of chromatin-remodeling factors involved in replication and how they affect DNA synthesis is largely unknown. Here we show that two highly conserved ATP-dependent chromatin-remodeling complexes in Saccharomyces cerevisiae, Isw2 and Ino80, function in parallel to promote replication fork progression. As a result, Isw2 and Ino80 have especially important roles for replication of late-replicating regions during periods of replication stress. Both Isw2 and Ino80 complexes are enriched at sites of replication, suggesting that these complexes act directly to promote fork progression. These findings identify ATP-dependent chromatin-remodeling complexes that promote DNA replication and define a specific stage of replication that requires remodeling for normal function.
真核生物的DNA复制机制在S期必须穿过基因组中的每个核小体。由于核小体通常会抑制依赖DNA的过程，染色质结构必须进行广泛的重组以促进DNA合成。然而，参与复制的染色质重塑因子的身份以及它们如何影响DNA合成在很大程度上尚不清楚。在这里，我们表明酿酒酵母中的两种高度保守的依赖ATP的染色质重塑复合物Isw2和Ino80并行发挥作用，以促进复制叉的进展。因此，Isw2和Ino80在复制应激期间对晚期复制区域的复制具有特别重要的作用。Isw2和Ino80复合物都在复制位点富集，这表明这些复合物直接作用以促进叉的进展。这些发现确定了促进DNA复制的依赖ATP的染色质重塑复合物，并定义了复制的一个特定阶段，该阶段需要重塑以实现正常功能。
