Deregulation of cyclin E in human cells interferes with prereplication complex assembly.
Deregulation of cyclin E in human cells interferes with prereplication complex assembly.
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DOI：
10.1083/jcb.200404092
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发表时间：
2004-06-21
期刊：
影响因子：
--
通讯作者：
Reed SI
中科院分区：
文献类型：
--
作者：
Ekholm-Reed S;Méndez J;Tedesco D;Zetterberg A;Stillman B;Reed SI
细胞周期蛋白 E 表达失调与多种人类恶性肿瘤有关。对组成性表达细胞周期蛋白 E 的细胞中 DNA 复制的分析表明，复制的起始和可能的叉运动受到严重损害，其水平与在肿瘤来源的细胞系子集中观察到的水平相似。这些细胞在末期和早期 G1 期间将起始蛋白 Mcm4、Mcm7 和较小程度的 Mcm2 装载到染色质上时表现出特定的缺陷，此时通常招募 Mcm2-7 来许可复制起点。由于微型染色体维持复合物蛋白被认为以异六聚体的形式发挥作用，Mcm2、Mcm4 和 Mcm7 耗尽的复合物的负载可能是在细胞周期蛋白 E 失调的细胞中观察到的 S 期缺陷的基础，这与微型染色体维持复合物蛋白在复制起始和分叉运动中的作用一致。细胞周期蛋白 E 介导的 DNA 复制损伤为细胞周期蛋白 E 失调导致的染色体不稳定提供了潜在机制。
Deregulation of cyclin E expression has been associated with a broad spectrum of human malignancies. Analysis of DNA replication in cells constitutively expressing cyclin E at levels similar to those observed in a subset of tumor-derived cell lines indicates that initiation of replication and possibly fork movement are severely impaired. Such cells show a specific defect in loading of initiator proteins Mcm4, Mcm7, and to a lesser degree, Mcm2 onto chromatin during telophase and early G1 when Mcm2–7 are normally recruited to license origins of replication. Because minichromosome maintenance complex proteins are thought to function as a heterohexamer, loading of Mcm2-, Mcm4-, and Mcm7-depleted complexes is likely to underlie the S phase defects observed in cyclin E–deregulated cells, consistent with a role for minichromosome maintenance complex proteins in initiation of replication and fork movement. Cyclin E–mediated impairment of DNA replication provides a potential mechanism for chromosome instability observed as a consequence of cyclin E deregulation.
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DOI：
10.1046/j.1432-1327.1999.00613.x
发表时间：
1999-09-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
Findeisen, M;El-Denary, M;Strausfeld, U
通讯作者：
Strausfeld, U
影响因子：
5.3
作者：
Ekholm, SV;Zickert, P;Zetterberg, A
通讯作者：
Zetterberg, A
影响因子：
6.4
作者：
Erlandsson, F;Wählby, C;Zetterberg, A
通讯作者：
Zetterberg, A
影响因子：
64.5
作者：
KRISHNA, TSR;KONG, XP;KURIYAN, J
通讯作者：
KURIYAN, J
影响因子：
11.4
作者：
Coue, M;Kearsey, SE;Mechali, M
通讯作者：
Mechali, M