真核细胞中DNA复制起始位点许可的机制。

Mechanisms for licensing origins of DNA replication in eukaryotic cells.

作者信息

Stillman Bruce, Diffley John F X, Iwasa Janet H

机构信息

Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA.

Chromosome Replication Laboratory, The Francis Crick Institute, London, UK.

出版信息

Nat Struct Mol Biol. 2025 Jun 30. doi: 10.1038/s41594-025-01587-5.

DOI:10.1038/s41594-025-01587-5

PMID:40588663

Abstract

The initiation of DNA replication in eukaryotic cells begins with the assembly of pre-replicative complexes (pre-RCs) at many sites along each chromosome during the G1 phase of the cell cycle. Pre-RCs license each chromosome for duplication during S phase and mark the origins of DNA replication. In this Review, we discuss and contextualize recent findings identifying the mechanisms of origin recognition and pre-RC assembly mediated by the origin recognition complex (ORC), Cdc6 and the Mcm2-Mcm7 (Mcm2-7) hexamer bound to Cdt1. We also present comprehensive videos that demonstrate the multiple mechanisms for pre-RC assembly and compare the structures of the complexes involved in human and Saccharomyces cerevisiae cells.

摘要

真核细胞中DNA复制的起始始于细胞周期G1期沿每条染色体多个位点上预复制复合体（pre-RC）的组装。预复制复合体许可每条染色体在S期进行复制，并标记DNA复制起点。在本综述中，我们讨论并结合近期的研究发现，这些发现确定了由起源识别复合体（ORC）、Cdc6以及与Cdt1结合的Mcm2-Mcm7（Mcm2-7）六聚体介导的复制起点识别和预复制复合体组装机制。我们还展示了全面的视频，这些视频展示了预复制复合体组装的多种机制，并比较了人类和酿酒酵母细胞中相关复合体的结构。