Homologous recombination (HR) is a critical pathway for maintaining genomic integrity, involved in both meiosis and DNA repair. It is essential for accurate chromosome segregation during meiosis and for repairing complex DNA damages, including double-stranded breaks, interstrand crosslinks, and DNA gaps. However, unrestrained HR can lead to genome rearrangements and genomic instability. The regulation of HR is complex and involves multiple levels of positive and negative control, including reversible post-translational modifications such as phosphorylation, ubiquitylation, and sumoylation. Key regulatory points include the formation and disruption of the Rad51-ssDNA filament, the resection of DNA double-stranded breaks, and the resolution of double Holliday junctions (dHJs). Post-translational modifications of proteins involved in these processes, such as Sae2/CtIP, BRCA2, and Sgs1/BLM, play crucial roles in modulating HR activity. The reversible nature of these intermediates suggests that HR achieves flexibility and robustness by proceeding through meta-stable, reversible stages. Additionally, mismatch repair (MMR) helps discriminate homologous from non-homologous sequences, ensuring that HR occurs between perfectly homologous sequences. The regulation of HR is a dynamic process that involves the interplay of various proteins and pathways, ultimately contributing to the accuracy and fidelity of DNA repair.Homologous recombination (HR) is a critical pathway for maintaining genomic integrity, involved in both meiosis and DNA repair. It is essential for accurate chromosome segregation during meiosis and for repairing complex DNA damages, including double-stranded breaks, interstrand crosslinks, and DNA gaps. However, unrestrained HR can lead to genome rearrangements and genomic instability. The regulation of HR is complex and involves multiple levels of positive and negative control, including reversible post-translational modifications such as phosphorylation, ubiquitylation, and sumoylation. Key regulatory points include the formation and disruption of the Rad51-ssDNA filament, the resection of DNA double-stranded breaks, and the resolution of double Holliday junctions (dHJs). Post-translational modifications of proteins involved in these processes, such as Sae2/CtIP, BRCA2, and Sgs1/BLM, play crucial roles in modulating HR activity. The reversible nature of these intermediates suggests that HR achieves flexibility and robustness by proceeding through meta-stable, reversible stages. Additionally, mismatch repair (MMR) helps discriminate homologous from non-homologous sequences, ensuring that HR occurs between perfectly homologous sequences. The regulation of HR is a dynamic process that involves the interplay of various proteins and pathways, ultimately contributing to the accuracy and fidelity of DNA repair.