In eukaryotes, DNA replication progresses through a finely orchestrated temporal and spatial program. The 3D genome structure and nuclear architecture have recently emerged as fundamental determinants of the replication program. Factors with established roles in replication have been recognized as genome organization regulators. Exploiting paradigms from yeasts and mammals, we discuss how DNA replication is regulated in time and space through DNA-associated trans-acting factors, diffusible limiting replication initiation factors, higher-order chromatin folding, dynamic origin localization, and specific nuclear microenvironments. We present an integrated model for the regulation of DNA replication in 3D and highlight the importance of accurate spatio-temporal regulation of DNA replication in physiology and disease.

在真核生物中，DNA复制通过精心设计的时空程序进行。3D基因组结构和核结构最近已成为复制程序的基本决定因素。在复制中具有确定作用的因素已被认为是基因组组织调节剂。利用酵母和哺乳动物的范例，我们讨论了如何通过与DNA相关的反转录来在时间和空间上调节DNA复制。作用因子，可扩散的限制性复制起始因子，高级染色质折叠，动态原点定位和特定的核微环境。我们提出了3D中DNA复制调控的集成模型，并强调了在生理和疾病中进行DNA复制的精确时空调控的重要性。