酵母 Pif1 DNA 解旋酶促进 G-四链体基序的 DNA 复制。
DNA replication through G-quadruplex motifs is promoted by the Saccharomyces cerevisiae Pif1 DNA helicase.
机构信息
Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
出版信息
Cell. 2011 May 27;145(5):678-91. doi: 10.1016/j.cell.2011.04.015.
Abstract
G-quadruplex (G4) DNA structures are extremely stable four-stranded secondary structures held together by noncanonical G-G base pairs. Genome-wide chromatin immunoprecipitation was used to determine the in vivo binding sites of the multifunctional Saccharomyces cerevisiae Pif1 DNA helicase, a potent unwinder of G4 structures in vitro. G4 motifs were a significant subset of the high-confidence Pif1-binding sites. Replication slowed in the vicinity of these motifs, and they were prone to breakage in Pif1-deficient cells, whereas non-G4 Pif1-binding sites did not show this behavior. Introducing many copies of G4 motifs caused slow growth in replication-stressed Pif1-deficient cells, which was relieved by spontaneous mutations that eliminated their ability to form G4 structures, bind Pif1, slow DNA replication, and stimulate DNA breakage. These data suggest that G4 structures form in vivo and that they are resolved by Pif1 to prevent replication fork stalling and DNA breakage.
摘要
G-四链体 (G4) DNA 结构是由非经典的 G-G 碱基对稳定形成的四链二级结构。通过全基因组染色质免疫沉淀来确定多功能酿酒酵母 Pif1 DNA 解旋酶的体内结合位点，Pif1 是体外 G4 结构的有效解旋酶。G4 基序是高可信度 Pif1 结合位点的重要子集。在这些基序附近，复制速度会减慢，并且在 Pif1 缺失的细胞中容易断裂，而非 G4 Pif1 结合位点则没有这种行为。在复制压力下，引入许多 G4 基序会导致 Pif1 缺失的细胞生长缓慢，而自发突变消除了它们形成 G4 结构、结合 Pif1、减缓 DNA 复制和刺激 DNA 断裂的能力，从而缓解了这种情况。这些数据表明 G4 结构在体内形成，并且它们被 Pif1 解决，以防止复制叉停滞和 DNA 断裂。
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