California Institute of Technology, Pasadena, CA USA.
Cell Cycle. 2011 May 15;10(10):1690-8. doi: 10.4161/cc.10.10.15643.
Dna2 is a dual polarity exo/endonuclease, and 5' to 3' DNA helicase involved in Okazaki Fragment Processing (OFP) and Double-Strand Break (DSB) Repair. In yeast, DNA2 is an essential gene, as expected for a DNA replication protein. Suppression of the lethality of dna2Δ mutants has been found to occur by two mechanisms: overexpression of RAD27 (scFEN1) , encoding a 5' to 3' exo/endo nuclease that processes Okazaki fragments (OFs) for ligation, or deletion of PIF1, a 5' to 3' helicase involved in mitochondrial recombination, telomerase inhibition and OFP. Mapping of a novel, spontaneously arising suppressor of dna2Δ now reveals that mutation of rad9 and double mutation of rad9 mrc1 can also suppress the lethality of dna2Δ mutants. Interaction of dna2Δ and DNA damage checkpoint mutations provides insight as to why dna2Δ is lethal but rad27Δ is not, even though evidence shows that Rad27 (ScFEN1) processes most of the Okazaki fragments, while Dna2 processes only a subset.
DNA2 是一种具有双极性外切/内切核酸酶和 5' 到 3' DNA 解旋酶活性的酶，参与冈崎片段加工（OFP）和双链断裂（DSB）修复。在酵母中，DNA2 是一种必需基因，这与 DNA 复制蛋白的功能相符。通过两种机制可以抑制 dna2Δ 突变体的致死性：RAD27（scFEN1）的过表达，RAD27 编码一种 5' 到 3' 外切/内切核酸酶，可对冈崎片段（OFs）进行加工以进行连接，或 PIF1 的缺失，PIF1 是一种参与线粒体重组、端粒酶抑制和 OFP 的 5' 到 3' 解旋酶。现在对一种新的自发出现的 dna2Δ 抑制因子进行定位，发现 rad9 的突变和 rad9 mrc1 的双突变也可以抑制 dna2Δ 突变体的致死性。DNA2Δ 和 DNA 损伤检查点突变的相互作用揭示了为什么 dna2Δ 是致命的，而 rad27Δ 却不是，尽管有证据表明 Rad27（ScFEN1）处理了大部分冈崎片段，而 Dna2 仅处理其中的一部分。
