Functional cooperation between FACT and MCM is coordinated with cell cycle and differential complex formation.
Functional cooperation between FACT and MCM is coordinated with cell cycle and differential complex formation.
复制标题
DOI：
10.1186/1423-0127-17-11
复制
发表时间：
2010-02-16
影响因子：
11
通讯作者：
Lee SC
中科院分区：
文献类型：
--
作者：
Tan BC;Liu H;Lin CL;Lee SC
FACT和MCM解旋酶复合物之间的功能合作构成了DNA复制起始过程中不可或缺的一步。然而，FACT和MCM的适当功能相互作用的基础调节模式知之甚少。在这里，我们提出的证据表明，这种相互作用是协调与细胞周期的进展和差分复合物的形成。我们首先证明了两个不同的FACT-MCM的存在，FACT-MCM 2/4/6/7和FACT-MCM 2/3/4/5。这两种复合物都具有DNA解旋活性，并受到细胞周期依赖性酶促调节。有趣的是，功能属性的分析进一步表明，它们在不同的，可能是连续的，在起点建立和复制启动的步骤。此外，我们表明，磷酸化概况的FACT-MCM 4经历了细胞周期依赖性的变化，这是直接相关的FACT-MCM解旋酶复合物的催化活性。最后，在四级结构水平上，FACT和MCM复合物之间的物理相互作用通常取决于持续的细胞周期，并在进入S期后进一步稳定。有丝分裂周期的停止破坏了复合体的形成，并可能导致协调和活动受损。总之，我们的研究结果关联FACT-MCM功能和时间与S期和DNA复制。他们进一步证明，对DNA复制本质上重要的酶活性在各种水平上受到严格控制，从而确保细胞周期的适当进展以及退出，并最终确保整倍体基因平衡。
Functional cooperation between FACT and the MCM helicase complex constitutes an integral step during DNA replication initiation. However, mode of regulation that underlies the proper functional interaction of FACT and MCM is poorly understood. Here we present evidence indicating that such interaction is coordinated with cell cycle progression and differential complex formation. We first demonstrate the existence of two distinct FACT-MCM subassemblies, FACT-MCM2/4/6/7 and FACT-MCM2/3/4/5. Both complexes possess DNA unwinding activity and are subject to cell cycle-dependent enzymatic regulation. Interestingly, analysis of functional attributes further suggests that they act at distinct, and possibly sequential, steps during origin establishment and replication initiation. Moreover, we show that the phosphorylation profile of the FACT-associated MCM4 undergoes a cell cycle-dependent change, which is directly correlated with the catalytic activity of the FACT-MCM helicase complexes. Finally, at the quaternary structure level, physical interaction between FACT and MCM complexes is generally dependent on persistent cell cycle and further stabilized upon S phase entry. Cessation of mitotic cycle destabilizes the complex formation and likely leads to compromised coordination and activities. Together, our results correlate FACT-MCM functionally and temporally with S phase and DNA replication. They further demonstrate that enzymatic activities intrinsically important for DNA replication are tightly controlled at various levels, thereby ensuring proper progression of, as well as exit from, the cell cycle and ultimately euploid gene balance.
登录
查看更多内容
影响因子：
14.9
作者：
Partington, GA;Patient, RK
通讯作者：
Patient, RK
影响因子：
4.8
作者：
Tan, BCM;Lee, SC
通讯作者：
Lee, SC
影响因子：
4.8
作者：
Lee, JK;Hurwitz, J
通讯作者：
Hurwitz, J
影响因子：
21.3
作者：
Gambus, A;Jones, RC;Labib, K
通讯作者：
Labib, K
影响因子：
4.8
作者：
Burke, TW;Cook, JG;Nevins, JR
通讯作者：
Nevins, JR