Integrated Program in Cellular, Molecular, and Biomedical Studies, Columbia University Irving Medical Center, New York, NY 10032, United States; Department of Microbiology & Immunology, Columbia University Irving Medical Center, New York, NY 10032, United States.
Department of Microbiology & Immunology, Columbia University Irving Medical Center, New York, NY 10032, United States; Program in Biological Sciences, Columbia University, New York, NY 10027, United States.
DNA Repair (Amst). 2024 Oct;142:103753. doi: 10.1016/j.dnarep.2024.103753. Epub 2024 Aug 16.
DNA replication stress is one of the primary causes of genome instability. In response to replication stress, cells can employ replication restart mechanisms that rely on homologous recombination to resume replication fork progression and preserve genome integrity. In this review, we provide an overview of various methods that have been developed to induce site-specific replication fork stalling or collapse in eukaryotic cells. In particular, we highlight recent studies of mechanisms of replication-associated recombination resulting from site-specific protein-DNA barriers and single-strand breaks, and we discuss the contributions of these findings to our understanding of the consequences of these forms of stress on genome stability.
DNA 复制压力是基因组不稳定的主要原因之一。为了应对复制压力,细胞可以利用依赖同源重组的复制重起始机制来恢复复制叉的推进,从而维持基因组的完整性。在这篇综述中,我们概述了已开发的各种方法,这些方法可用于诱导真核细胞中特定位置的复制叉停滞或崩溃。特别地,我们强调了最近关于由特定位置的蛋白-DNA 障碍和单链断裂引起的复制相关重组机制的研究,并讨论了这些发现对我们理解这些形式的压力对基因组稳定性的影响的贡献。