Shankar Srihari, Enemark Eric J
Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, 4301 West Markham Street, Slot 516, Little Rock, AR 72205, USA.
Acta Crystallogr F Struct Biol Commun. 2025 May 1;81(Pt 5):207-215. doi: 10.1107/S2053230X25003085. Epub 2025 Apr 16.
DNA replication is tightly regulated to ensure genomic stability and prevent several diseases, including cancers. Eukaryotes and archaea partly achieve this regulation by strictly controlling the activation of hexameric minichromosome maintenance (MCM) helicase rings that unwind DNA during its replication. In eukaryotes, MCM activation critically relies on the sequential recruitment of the essential factors Cdc45 and a tetrameric GINS complex at the onset of the S-phase to generate a larger CMG complex. We present the crystal structure of the tetrameric GINS complex from the archaeal organism Saccharolobus solfataricus (Sso) to reveal a core structure that is highly similar to the previously determined GINS core structures of other eukaryotes and archaea. Using molecular modeling, we illustrate that a subdomain of SsoGINS would need to move to accommodate known interactions of the archaeal GINS complex and to generate a SsoCMG complex analogous to that of eukaryotes.
DNA复制受到严格调控,以确保基因组稳定性并预防包括癌症在内的多种疾病。真核生物和古细菌部分地通过严格控制六聚体微小染色体维持(MCM)解旋酶环的激活来实现这种调控,该解旋酶环在DNA复制过程中解开DNA。在真核生物中,MCM激活关键依赖于在S期开始时依次招募必需因子Cdc45和四聚体GINS复合物,以生成更大的CMG复合物。我们展示了来自古细菌嗜热栖热菌(Saccharolobus solfataricus,Sso)的四聚体GINS复合物的晶体结构,以揭示一种核心结构,该结构与先前确定的其他真核生物和古细菌的GINS核心结构高度相似。通过分子建模,我们表明SsoGINS的一个亚结构域需要移动以适应古细菌GINS复合物的已知相互作用,并生成类似于真核生物的SsoCMG复合物。