Mcm10 and And-1/CTF4 recruit DNA polymerase alpha to chromatin for initiation of DNA replication.
Mcm10 and And-1/CTF4 recruit DNA polymerase alpha to chromatin for initiation of DNA replication.
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DOI：
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发表时间：
2007
影响因子：
10.5
通讯作者：
Wenge Zhu;C. Ukomadu;S. Jha;T. Senga;S. Dhar;J. Wohlschlegel;L. Nutt;S. Kornbluth;Anindya Dutta
中科院分区：
文献类型：
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作者：
Wenge Zhu;C. Ukomadu;S. Jha;T. Senga;S. Dhar;J. Wohlschlegel;L. Nutt;S. Kornbluth;Anindya Dutta
MCM2-7解旋酶复合体在细胞周期的G1期被装载在DNA复制起点上，以允许起点在S期进行复制。引发物引物-聚合酶复合物DNA聚合酶α (pol α)是如何到达起点的尚不清楚。我们发现and -1/Ctf4（染色体传递保真度4）与Mcm10相互作用，Mcm10与MCM2-7相关联，并与DNA pol α的p180亚基相互作用。and -1在哺乳动物细胞中对DNA合成和p180的稳定性至关重要。在爪蟾卵提取物中，and -1在Mcm10之后被装载到染色质上，同时与DNA pol - α一起，并且是高效DNA合成所必需的。Mcm10是装载and -1的染色质所必需的，破坏Mcm10- and -1相互作用的抗体会干扰装载and -1和pol - α，抑制DNA合成。因此，and -1/Ctf4是一种新的复制起始因子，它将MCM2-7解旋酶和DNA pol α -引物酶复合物结合在一起，类似于解旋酶和引物酶或解旋酶和聚合酶之间的连接物，在细菌复制机制中可见。这一发现也增加了复制起始和姐妹染色单体内聚之间的联系。
The MCM2-7 helicase complex is loaded on DNA replication origins during the G1 phase of the cell cycle to license the origins for replication in S phase. How the initiator primase-polymerase complex, DNA polymerase alpha (pol alpha), is brought to the origins is still unclear. We show that And-1/Ctf4 (Chromosome transmission fidelity 4) interacts with Mcm10, which associates with MCM2-7, and with the p180 subunit of DNA pol alpha. And-1 is essential for DNA synthesis and the stability of p180 in mammalian cells. In Xenopus egg extracts And-1 is loaded on the chromatin after Mcm10, concurrently with DNA pol alpha, and is required for efficient DNA synthesis. Mcm10 is required for chromatin loading of And-1 and an antibody that disrupts the Mcm10-And-1 interaction interferes with the loading of And-1 and of pol alpha, inhibiting DNA synthesis. And-1/Ctf4 is therefore a new replication initiation factor that brings together the MCM2-7 helicase and the DNA pol alpha-primase complex, analogous to the linker between helicase and primase or helicase and polymerase that is seen in the bacterial replication machinery. The discovery also adds to the connection between replication initiation and sister chromatid cohesion.