Yet another job for Dna2: Checkpoint activation.
Yet another job for Dna2: Checkpoint activation.
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DOI：
10.1016/j.dnarep.2015.04.009
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发表时间：
2015-08
期刊：
影响因子：
3.8
通讯作者：
Burgers PM
中科院分区：
文献类型：
--
作者：
Wanrooij PH;Burgers PM
Mec 1（人类ATR）是酿酒酵母中负责响应复制应激和DNA损伤的检查点激活的主要激酶。检查点启动需要特异性激活剂刺激Mec 1激酶活性。酵母中检查点起始的复杂性随着细胞周期不同阶段期间染色体状态的复杂性而增加。在G1期，检查点钳9-1-1对于Mec 1激酶的完全激活是必要的和足够的，而在G2/M期，稳健的检查点功能需要9-1-1和复制体组装蛋白Dpb 11（人TopBP 1）两者。第三个激活剂，DNA 2，特别是在S期刺激Mec 1激酶，并启动复制检查点。dna 2是一种必需的核酸解旋酶，它是冈崎片段成熟、双链断裂修复和保护停滞复制叉所必需的。值得注意的是，所有三种Mec 1激活剂都使用蛋白质的非结构化区域，包含两个至关重要的芳香残基，以激活Mec 1。这些检查点激活剂通道异常复制结构到检查点复合物的作用进行了讨论。
Mec1 (ATR in humans) is the principal kinase responsible for checkpoint activation in response to replication stress and DNA damage in Saccharomyces cerevisiae. Checkpoint initiation requires stimulation of Mec1 kinase activity by specific activators. The complexity of checkpoint initiation in yeast increases with the complexity of chromosomal states during the different phases of the cell cycle. In G1 phase, the checkpoint clamp 9-1-1 is both necessary and sufficient for full activation of Mec1 kinase whereas in G2/M, robust checkpoint function requires both 9-1-1 and the replisome assembly protein Dpb11 (human TopBP1). A third activator, Dna2, is employed specifically during S phase to stimulate Mec1 kinase and to initiate the replication checkpoint. Dna2 is an essential nuclease-helicase that is required for proper Okazaki fragment maturation, for double-strand break repair, and for protecting stalled replication forks. Remarkably, all three Mec1 activators use an unstructured region of the protein, containing two critically important aromatic residues, in order to activate Mec1. A role for these checkpoint activators in channeling aberrant replication structures into checkpoint complexes is discussed.