Sabelli P A, Burgess S R, Kush A K, Young M R, Shewry P R
IACR-Long Ashton Research Station, Department of Agricultural Sciences, University of Bristol, UK.
Mol Gen Genet. 1996 Aug 27;252(1-2):125-36. doi: 10.1007/BF02173212.
A central question in cell cycle regulation is how DNA replication is initiated and executed only once in each cell cycle. The cell cycle-regulated assembly of specific initiation protein complexes at chromosomal origins appears to specify the initial sites and timing of DNA replication, and to restrict this process to only one round in the somatic cell cycle. Among the enzymes involved in origin activation, the MCM proteins play a conserved key role. In particular, MCM3 homologues have been shown to be components of the DNA replication licensing activity in yeast and vertebrates. In spite of our detailed knowledge of the regulation of the initiation of DNA synthesis in yeast, there is virtually no information available on the molecules involved in origin activation in higher plants. We have isolated a cDNA from maize root apices, termed ROA (Replication Origin Activator), encoding a protein which shares a high degree of homology with the MCM3 subfamily of MCM proteins. Analysis of gene organisation by Southern blotting shows 2-4 copies per haploid genome of closely related ROA sequences and the presence of further less related sequences in a multigene family. The steady-state levels of ROA mRNA are under developmental control, being relatively high in proliferative tissues such as the root apex, the developing cob and the coleoptile, and are strongly correlated with that of the histone H4 transcript. In situ hybridisation analysis in the root apex reveals that ROA mRNA expression is limited to specific subpopulations of cycling cells, which is typical of cell cycle-regulated expression. The isolation of nearly identical sequences from barley and Arabidopsis by the polymerase chain reaction indicates that MCM-related proteins are conserved in higher plants.
细胞周期调控中的一个核心问题是,DNA复制如何在每个细胞周期中仅起始并执行一次。特定起始蛋白复合物在染色体起源处的细胞周期调控组装似乎决定了DNA复制的起始位点和时间,并将这一过程限制在体细胞周期中的一轮。在参与起源激活的酶中,MCM蛋白发挥着保守的关键作用。特别是,MCM3同源物已被证明是酵母和脊椎动物中DNA复制许可活性的组成部分。尽管我们对酵母中DNA合成起始的调控有详细了解,但关于高等植物中参与起源激活的分子几乎没有可用信息。我们从玉米根尖中分离出一个cDNA,称为ROA(复制起源激活因子),它编码一种与MCM蛋白的MCM3亚家族具有高度同源性的蛋白质。通过Southern杂交分析基因组织表明,单倍体基因组中每个有2 - 4个紧密相关的ROA序列拷贝,并且在一个多基因家族中存在其他相关性较低的序列。ROA mRNA的稳态水平受发育调控,在增殖组织如根尖、发育中的玉米穗轴和胚芽鞘中相对较高,并且与组蛋白H4转录本的水平密切相关。根尖的原位杂交分析表明,ROA mRNA表达仅限于循环细胞的特定亚群,这是细胞周期调控表达的典型特征。通过聚合酶链反应从大麦和拟南芥中分离出几乎相同的序列,表明与MCM相关的蛋白在高等植物中是保守的。