Homologous recombination (HR) is essential for accurate chromosome segregation during meiosis and for repairing complex DNA damage, including DNA double-stranded breaks, interstrand crosslinks, and DNA gaps. It is also crucial for maintaining genomic stability and preventing genome rearrangements. However, uncontrolled HR can lead to harmful outcomes like translocations and deletions. Therefore, HR must be tightly regulated to balance its beneficial and harmful effects. HR involves multiple mechanistic stages and proteins, including Rad51, Rad52, BRCA2, and others, which are subject to regulation through post-translational modifications such as phosphorylation, ubiquitylation, and sumoylation. These modifications help control the formation and disruption of HR intermediates, ensuring the pathway's flexibility and robustness. HR is regulated by the cell cycle and DNA damage response (DDR), with key regulatory points including DSB resection, Rad51 filament formation, and the balance between different HR sub-pathways like break-induced replication (BIR), synthesis-dependent strand annealing (SDSA), and double Holliday junction (dHJ) resolution. The regulation of HR is complex, involving multiple proteins and pathways that ensure accurate repair while minimizing genomic instability. Key regulatory mechanisms include the control of DSB resection by CDK-dependent phosphorylation of Sae2/CtIP, the role of DDR signaling in modulating HR, and the involvement of anti-recombinogenic proteins like Srs2 and BLM in preventing excessive recombination. The balance between HR and other repair pathways, such as non-homologous end joining (NHEJ) and translesion synthesis (TLS), is also crucial for maintaining genomic integrity. Overall, HR is a highly regulated process that ensures accurate DNA repair and genomic stability, with multiple checkpoints and regulatory mechanisms that prevent errors and promote robustness.Homologous recombination (HR) is essential for accurate chromosome segregation during meiosis and for repairing complex DNA damage, including DNA double-stranded breaks, interstrand crosslinks, and DNA gaps. It is also crucial for maintaining genomic stability and preventing genome rearrangements. However, uncontrolled HR can lead to harmful outcomes like translocations and deletions. Therefore, HR must be tightly regulated to balance its beneficial and harmful effects. HR involves multiple mechanistic stages and proteins, including Rad51, Rad52, BRCA2, and others, which are subject to regulation through post-translational modifications such as phosphorylation, ubiquitylation, and sumoylation. These modifications help control the formation and disruption of HR intermediates, ensuring the pathway's flexibility and robustness. HR is regulated by the cell cycle and DNA damage response (DDR), with key regulatory points including DSB resection, Rad51 filament formation, and the balance between different HR sub-pathways like break-induced replication (BIR), synthesis-dependent strand annealing (SDSA), and double Holliday junction (dHJ) resolution. The regulation of HR is complex, involving multiple proteins and pathways that ensure accurate repair while minimizing genomic instability. Key regulatory mechanisms include the control of DSB resection by CDK-dependent phosphorylation of Sae2/CtIP, the role of DDR signaling in modulating HR, and the involvement of anti-recombinogenic proteins like Srs2 and BLM in preventing excessive recombination. The balance between HR and other repair pathways, such as non-homologous end joining (NHEJ) and translesion synthesis (TLS), is also crucial for maintaining genomic integrity. Overall, HR is a highly regulated process that ensures accurate DNA repair and genomic stability, with multiple checkpoints and regulatory mechanisms that prevent errors and promote robustness.