真核生物DNA复制起始受到机体的严格调控。在G1期，复制解旋酶的核心组分Mcm2-7以无活性的双六聚体构象 (double hexamer，DH) 装载到复制原点形成pre-RC。当细胞进入G1/S期，激酶S-CDK和DDK行使其功能，将Cdc45、GINS等DNA复制因子招募至pre-RC形成pre-IC。直至S期，pre-IC在Mcm10、DDK等解旋酶激活因子的作用下，形成具有解旋酶活性的Cdc45-Mcm2-7-GINS (CMG) 复合体，起始DNA复制。迄今，Mcm10激活复制解旋酶的具体机制尚不明确。本项目拟通过冷冻电镜技术解析Mcm10与Mcm2-7双六聚体形成的超复合体（Mcm10-DH）的高分辨率结构。并结合遗传与生化手段，对Mcm10-DH互作界面进行突变或互补分析，探讨Mcm10-DH构象与解旋酶活性之间的关系，将有助于揭示解旋酶Mcm2-7激活的分子机制。

The initiation of DNA replication is strictly regulated in eukaryotes. The core components of the replicative helicase，Mcm2-7，are loaded as an inactive double hexamer (DH) onto origins，to form the pre-RC during G1 phase. After the formation of pre-RC，the Cdc45，GINS and other replication factors assemble on origins，and the pre-IC is formed. This reaction requires S-CDK and DDK. Once the pre-IC is activated by MCM10 ,DDK and other activators，the active Cdc45-Mcm2-7-GINS complex is formed，and then DNA replication fork is established. So far，the molecular mechanisms of the activation of DNA replicative helicase Mcm2-7 by Mcm10 remains elusive. We’ll resolve structures of the MCM10-DH super complex by cryo-electron microscopy. Combines with genetic and biochemical approaches，mutations of Mcm10-DH interfacial interface will be constructed to explore the relationship between Mcm10-DH conformation and helicase activity，which may shed light on the molecular mechanism of Mcm2-7 activation.