🏆 Foundational Paper

From structure to mechanism-understanding initiation of DNA replication.

Riera Alberto, Barbon Marta, Noguchi Yasunori, Reuter L Maximilian, Schneider Sarah, Speck Christian

📰 Genes & development 📅 2017 📊 105 citations

Abstract

DNA replication results in the doubling of the genome prior to cell division. This process requires the assembly of 50 or more protein factors into a replication fork. Here, we review recent structural and biochemical insights that start to explain how specific proteins recognize DNA replication origins, load the replicative helicase on DNA, unwind DNA, synthesize new DNA strands, and reassemble chromatin. We focus on the minichromosome maintenance (MCM2-7) proteins, which form the core of the eukaryotic replication fork, as this complex undergoes major structural rearrangements in order to engage with DNA, regulate its DNA-unwinding activity, and maintain genome stability.

🔬 Techniques

🧬 Organisms

🧪 Sample Preparation

💾 Data Repositories

🏛️ Research Organizations (ROR)

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📊 Figures

Figure 1.

Eukaryotic initiation of DNA replication. Relevant complexes that have been characterized by electron microscopy are shown in surface view. ( A ) ORC is chromatin bound throughout the cell cycle (Elec...

Figure 2.

Origin recognition. ( A ) The domain and structural organization of Orc and Cdc6 proteins. The initiator-specific motif region of the AAA-RecA domain is indicated in red. ( B , left ) The OCCM structu...

Figure 3.

MCM2u20137 helicase function arises from its architecture. ( A ) Domain structure of an Mcm protein with its four domains: A, oligonucleotide binding (OB), ATPase, and WHD. The color-coding for specif...

Figure 4.

Structural changes in Mcm subunits dictate their function. Cartoon-style atomic models of OCCM ( A ; PDB: 5UDB), MCM2u20137 DH ( B ; PDB: 3JA8), and CMG bound to a replication fork ( C ; PDB: 5U8S). (...

Figure 5.

MCM2u20137 DNA interactions within the OCCM, DH, and CMG complexes. ( A ) Detailed structural overlays of selected budding yeast (gray; PDB: 5U8S; Mcm2 of CMG bound to a replication fork) and S. solfa...

Figure 6.

MCM2u20137 proteinu2013protein interactions in the context of OCCM and CMG. Interactions between the Mcm subunits (in gray gradient) and the Orc subunits (Orc1 in green, Orc2 in brown, Orc3 in salmon,...

Figure images are served from the NIH/NLM PubMed Central Open Access Subset or Europe PMC; copyright remains with the publishers and authors.

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🏛️ Imperial College London

💬 Discussion

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