Induction of homologous recombination by site-specific replication stress

• Published in: DNA repair 2024-10, Vol.142, p.103753, Article 103753
• Main Authors: Triplett, Marina K., Johnson, Matthew J., Symington, Lorraine S.
• Format: Article
• Language: English
• Subjects: Animals; DNA - metabolism; DNA Breaks, Single-Stranded; DNA Damage; DNA Replication; Double-strand break (DSB); Genomic Instability; Homologous Recombination; Humans; Rad51; Replication restart; Replication stress; Stress, Physiological
• ISSN: 1568-7864; 1568-7856; 1568-7856
• DOI: 10.1016/j.dnarep.2024.103753

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. •Homologous recombination is required tomaintain genome integrity in response to replication stress.•Site-specific, protein-induced replicationfork barriers induce local Rad51-dependent recombination.•Replication fork collision with a nick canproduce one-ended or two-ended double-strand breaks.•Replication-dependent DSBs are repaired byhomologous recombination with the sister chromatid.