Efficient Initiation of DNA Replication in Eukaryotes Requires Dpb11/TopBP1-GINS Interaction
Efficient Initiation of DNA Replication in Eukaryotes Requires Dpb11/TopBP1-GINS Interaction
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DOI：
10.1128/mcb.00431-13
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发表时间：
2013-05
影响因子：
5.3
通讯作者：
S. Tanaka;Y. Komeda;Toshiko Umemori;Y. Kubota;H. Takisawa;H. Araki
中科院分区：
文献类型：
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作者：
S. Tanaka;Y. Komeda;Toshiko Umemori;Y. Kubota;H. Takisawa;H. Araki
摘要Dpb 11/Cut 5/TopBP 1在进化上保守，对于真核生物DNA复制的启动至关重要。芽殖酵母Saccharomyces cerevisiae的Dpb 11具有四个BRCT结构域（BRCT 1至-4）。N端对（BRCT 1和-2）和C端对（BRCT 3和-4）分别与细胞周期蛋白依赖性激酶（CDK）磷酸化的Sld 3和Sld 2结合。这些磷酸化依赖的相互作用触发DNA复制的启动。Dpb 11的BRCT 1和-2以及BRCT 3和-4被一小段约100个氨基酸分开。目前尚不清楚这一BRCT间区域是否在DNA复制中起作用。在这里，我们表明，间BRCT区域是一个GINS相互作用的结构域，是必不可少的细胞生长和突变，在这一领域的原因在芽殖酵母复制缺陷。我们在脊椎动物直系同源基因TopBP 1中发现了相应的区域，并表明相应的区域也与GINS相互作用，并且是有效DNA复制所必需的。我们提出，Dpb 11的间BRCT区域是一个功能保守的GINS相互作用结构域，它对真核生物中DNA复制的启动非常重要。
ABSTRACT Dpb11/Cut5/TopBP1 is evolutionarily conserved and is essential for the initiation of DNA replication in eukaryotes. The Dpb11 of the budding yeast Saccharomyces cerevisiae has four BRCT domains (BRCT1 to -4). The N-terminal pair (BRCT1 and -2) and the C-terminal pair (BRCT3 and -4) bind to cyclin-dependent kinase (CDK)-phosphorylated Sld3 and Sld2, respectively. These phosphorylation-dependent interactions trigger the initiation of DNA replication. BRCT1 and -2 and BRCT3 and -4 of Dpb11 are separated by a short stretch of ∼100 amino acids. It is unknown whether this inter-BRCT region functions in DNA replication. Here, we showed that the inter-BRCT region is a GINS interaction domain that is essential for cell growth and that mutations in this domain cause replication defects in budding yeast. We found the corresponding region in the vertebrate ortholog, TopBP1, and showed that the corresponding region also interacts with GINS and is required for efficient DNA replication. We propose that the inter-BRCT region of Dpb11 is a functionally conserved GINS interaction domain that is important for the initiation of DNA replication in eukaryotes.