RecQL4 is required for the association of Mcm10 and Ctf4 with replication origins in human cells
RecQL4 is required for the association of Mcm10 and Ctf4 with replication origins in human cells
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DOI：
10.1080/15384101.2015.1007001
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发表时间：
2015-04-01
期刊：
影响因子：
4.3
通讯作者：
Lee, Joon-Kyu
中科院分区：
文献类型：
--
作者：
Im, Jun-Sub;Park, Soon-Young;Lee, Joon-Kyu
尽管RecQL4被证明是哺乳动物细胞DNA复制起始的必要条件，但其在起始过程中的作用尚不清楚。在这里，我们发现RecQL4是Mcm10和Ctf4的起点结合所必需的，它们的物理相互作用和与复制起点的关联是由CDK和DDK活性的协同作用控制的。尽管依赖recql4的Mcm10和Ctf4与染色质的结合可以在没有复制前复合体的情况下发生，但它们与复制起源的关联需要复制前复合体和CDK和DDK活性的存在。它们与复制起点和物理相互作用的关联也是DNA损伤检查点途径的目标，这些途径阻止DNA在复制起点开始复制。综上所述，依赖recql4的Mcm10和Ctf4与复制起源的关联似乎是人类细胞中DNA复制起始的第一个重要步骤，由S期促进激酶和检查点途径控制。
Though RecQL4 was shown to be essential for the initiation of DNA replication in mammalian cells, its role in initiation is poorly understood. Here, we show that RecQL4 is required for the origin binding of Mcm10 and Ctf4, and their physical interactions and association with replication origins are controlled by the concerted action of both CDK and DDK activities. Although RecQL4-dependent binding of Mcm10 and Ctf4 to chromatin can occur in the absence of pre-replicative complex, their association with replication origins requires the presence of the pre-replicative complex and CDK and DDK activities. Their association with replication origins and physical interactions are also targets of the DNA damage checkpoint pathways which prevent initiation of DNA replication at replication origins. Taken together, the RecQL4-dependent association of Mcm10 and Ctf4 with replication origins appears to be the first important step controlled by S phase promoting kinases and checkpoint pathways for the initiation of DNA replication in human cells.