Pre-replication complex organization in the atypical DNA replication cycle of Plasmodium falciparum:: Characterization of the mini-chromosome maintenance (MCM) complex formation
Pre-replication complex organization in the atypical DNA replication cycle of Plasmodium falciparum:: Characterization of the mini-chromosome maintenance (MCM) complex formation
复制标题
DOI：
10.1016/j.molbiopara.2005.09.006
复制
发表时间：
2006-01-01
影响因子：
1.5
通讯作者：
Chakrabarti, D
中科院分区：
文献类型：
--
作者：
Patterson, S;Robert, C;Chakrabarti, D
疟原虫中细胞分裂的整体组织与在模式生物中观察到的相比是独特的，因为DNA在其生命周期的几个点上每个细胞周期复制不止一次。疟原虫基因组的测序还揭示了真核细胞周期机制的许多关键组分（例如Cdt 1，DDK和Cdc 45）的明显缺失，这些组分负责复制前复合物（pre-RC）的形成。我们的特点是恶性疟原虫微型染色体维持复合物（MCM），发挥了关键作用的前RC的RC过渡。与其他真核生物类似，疟原虫基因组编码六个MCM亚基。在这里，我们表明，表达水平的至少三个PfMCM亚基，同源的MCM 2，MCM 6和MCM 7，在红细胞内发育周期中的变化，峰值在鞭毛体和减少在环和滋养体阶段。PfMCM 2，6和7亚基相互作用，形成一个发育调控的复合物：这些相互作用是可检测的环和寄生虫，但不是在滋养体。PfMCM 2、6和7亚基在恶性疟原虫发育的所有红细胞内阶段均定位于胞浆和核浆组分中，在疟原虫中的核定位增加。只有PfMCM 6与所有生长阶段的染色质组分相关。没有磷酸化的PfMCM 2，6和7被检测到，但两个尚未确定的苏氨酸磷酸化的蛋白质存在于复杂的，其磷酸化的模式在寄生虫发育过程中的变化。(c)2005 Elsevier B. V.保留所有权利。
The overall organization of cell division in Plasmodium is unique compared to that observed in model organisms because DNA replicates more than once per cell cycle at several points of its life cycle. The sequencing of the Plasmodium genome has also revealed the apparent absence of many key components (e.g. Cdt1, DDK and Cdc45) of the eukaryotic cell cycle machinery that are responsible for the formation of the pre-replication complex (pre-RC). We have characterized the Plasmodium falciparum minichromosome maintenance complex (MCM) that plays a key role in the transition of pre-RC to the RC. Similar to other eukaryotes, the Plasmodium genome encodes six MCM subunits. Here, we show that expression levels of at least three of the PfMCM subunits, the homologues of MCM2, MCM6 and MCM7, change during the intraerythrocytic development cycle, peaking in schizont and decreasing in the ring and trophozoite stages. PfMCM2, 6 and 7 subunits interact with each other to form a developmentally regulated complex: these interactions are detectable in rings and schizonts, but not in trophozoites. PfMCM2, 6 and 7 subunits are localized in both cytosolic and nucleosolic fractions during all intraerythrocytic stages of P. falciparum development, with increased nuclear localization in schizonts. Only PfMCM6 is associated with the chromatin fraction at all stages of growth. No phosphorylation of PfMCM2, 6 and 7 was detected, but two as yet unidentified threonine-phosphosphorylated proteins were present in the complex, whose pattern of phosphorylation varied during parasite development. (c) 2005 Elsevier B.V. All rights reserved.