Orc6 involved in DNA replication, chromosome segregation, and cytokinesis
Orc6 involved in DNA replication, chromosome segregation, and cytokinesis
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DOI：
10.1126/science.1072802
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发表时间：
2002-08-09
期刊：
影响因子：
56.9
通讯作者：
Stillman, B
中科院分区：
文献类型：
--
作者：
Prasanth, SG;Prasanth, KV;Stillman, B
起源识别复合体（ORC）蛋白作为多蛋白预复制复合体组装的着陆点，是启动DNA复制所必需的。在有丝分裂过程中，人类ORC的最小亚基Orc6定位于着丝点和细胞周围的网状结构。当染色体在分裂后期分离时，网状结构沿着细胞分裂平面排列，一些Orc6在细胞分离前定位于中间体。通过小干扰RNA （siRNA）沉默Orc6的表达，导致细胞具有多极纺锤体，有丝分裂异常，形成多核细胞，DNA复制减少。长时间的Orc6耗竭导致细胞增殖减少和细胞死亡增加。这些结果暗示Orc6是协调染色体复制和分离与细胞分裂的重要基因。
Origin recognition complex (ORC) proteins serve as a landing pad for the assembly of a multiprotein prereplicative complex, which is required to initiate DNA replication. During mitosis, the smallest subunit of human ORC, Orc6, localizes to kinetochores and to a reticular-like structure around the cell periphery. As chromosomes segregate during anaphase, the reticular structures align along the plane of cell division and some Orc6 localizes to the midbody before cells separate. Silencing of Orc6 expression by small interfering RNA (siRNA) resulted in cells with multipolar spindles, aberrant mitosis, formation of multinucleated cells, and decreased DNA replication. Prolonged periods of Orc6 depletion caused a decrease in cell proliferation and increased cell death. These results implicate Orc6 as an essential gene that coordinates chromosome replication and segregation with cytokinesis.