Mcm10 and the MCM2-7 complex interact to initiate DNA synthesis and to release replication factors from origins.
Mcm10 and the MCM2-7 complex interact to initiate DNA synthesis and to release replication factors from origins.
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DOI：
10.1101/gad.14.8.913
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发表时间：
2000-04
影响因子：
10.5
通讯作者：
Lisa Homesley;Ming Lei;Yasuo Kawasaki;Sara L. Sawyer;Tim W. Christensen;B. Tye
中科院分区：
文献类型：
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作者：
Lisa Homesley;Ming Lei;Yasuo Kawasaki;Sara L. Sawyer;Tim W. Christensen;B. Tye
MCM 2 -7是由6个亚基组成的复合体，是复制前染色质的重要组成部分，在G（1）期组装在酿酒酵母复制起点。它也被认为是生长分叉处的进行性解旋酶。为了阐明MCM 2 -7在从起始到延伸复制的过渡过程中的作用，我们将我们的研究集中在Mcm 10上，Mcm 10是一种与MCM 2 -7复合物的成员物理相互作用的复制起始蛋白。我们表明，Mcm 10是一种染色质相关蛋白，介导的协会的MCM 2 -7复合物与复制起点。此外，Mcm 10和Mcm 7（MCM 2 -7复合物的一个亚基）之间的相互作用因Mcm 10或Mcm 7中的突变而减弱，从而抑制复制起始。令人惊讶的是，含有mcm 10 -1和mcm 7 -1（cdc 47 -1）等位基因的双突变体恢复了Mcm 10和Mcm 7之间的相互作用，并纠正了每个单突变体所表现出的所有缺陷，包括通常在mcm 10 -1细胞中观察到的复制起点处的复制叉停滞。两个独立分离的突变之间的缺陷的相互补偿是等位基因特异性的。这些结果表明，Mcm 10，像Mcm 7，是一个重要组成部分的复制前染色质和Mcm 10和Mcm 7之间的相互作用是必要的适当的复制启动和迅速释放的起源结合因子。
MCM2-7, a complex of six subunits, is an essential component of the prereplication chromatin that is assembled at Saccharomyces cerevisiae replication origins during G(1) phase. It is also believed to be the processive helicase at growing forks. To elucidate the action of MCM2-7 during the transition from initiation to elongation replication, we have focused our studies on Mcm10, a replication initiation protein that physically interacts with members of the MCM2-7 complex. We show that Mcm10 is a chromatin-associated protein that mediates the association of the MCM2-7 complex with replication origins. Furthermore, diminished interaction between Mcm10 and Mcm7, a subunit of the MCM2-7 complex, by a mutation in either Mcm10 or Mcm7 inhibits replication initiation. Surprisingly, a double mutant containing both the mcm10-1 and mcm7-1 (cdc47-1) alleles restores interaction between Mcm10 and Mcm7 and corrects all of the defects exhibited by each of the single mutants, including the stalling of replication forks at replication origins typically seen in mcm10-1 cells. This mutual compensation of defects between two independently isolated mutations is allele specific. These results suggest that Mcm10, like Mcm7, is a critical component of the prereplication chromatin and that interaction between Mcm10 and Mcm7 is required for proper replication initiation and prompt release of origin-bound factors.