滞后链成熟因子 Dna2 是复制检查点起始机制的一个组成部分。
Lagging strand maturation factor Dna2 is a component of the replication checkpoint initiation machinery.
机构信息
Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO 63110, USA.
出版信息
Genes Dev. 2013 Feb 1;27(3):313-21. doi: 10.1101/gad.204750.112. Epub 2013 Jan 25.
Abstract
Initiation of the DNA replication checkpoint in yeast is mainly mediated by Mec1 protein kinase, the ortholog of human ATR, while its homolog Tel1, the ortholog of human ATM, has a minor replication checkpoint function. Checkpoint initiation requires stimulation of Mec1 kinase activity by specific activators. Saccharomyces cerevisiae Dna2, a nuclease-helicase that is essential for Okazaki fragment maturation, is employed specifically during S phase to stimulate Mec1 kinase and initiate the replication checkpoint. Mutations (W128A and Y130A) in the unstructured N terminus of Dna2 abrogate its checkpoint function in vitro and in vivo. Dna2 shows partial redundancy for the replication checkpoint with checkpoint initiators 9-1-1 (S. cerevisiae Ddc1-Mec3-Rad17 and human Rad9-Rad1-Hus1) and Dpb11, the ortholog of human TopBP1. A triple mutant that eliminates the checkpoint functions of all three initiators abrogates the Mec1-dependent checkpoint.
摘要
酵母中 DNA 复制检查点的启动主要由 Mec1 蛋白激酶介导，该激酶是人类 ATR 的同源物，而其同源物 Tel1（人类 ATM 的同源物）则具有较小的复制检查点功能。检查点的启动需要特定的激活物来刺激 Mec1 激酶的活性。酿酒酵母 Dna2 是一种核酸酶-解旋酶，对于 Okazaki 片段的成熟是必不可少的，它专门在 S 期被用来刺激 Mec1 激酶并启动复制检查点。Dna2 的无结构 N 端中的突变（W128A 和 Y130A）在体外和体内都消除了其检查点功能。Dna2 与检查点起始因子 9-1-1（酿酒酵母 Ddc1-Mec3-Rad17 和人类 Rad9-Rad1-Hus1）和 Dpb11（人类 TopBP1 的同源物）具有部分冗余的复制检查点功能。消除这三个起始因子的检查点功能的三突变体消除了对 Mec1 的依赖性检查点。
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