The cell cycle is a crucial biological process that ensures the accurate replication and division of cells. It consists of G1, S, G2, and M phases, with the S phase being the DNA synthesis phase and the M phase involving mitosis. R-loops, which are three-stranded structures formed during transcription, can interfere with DNA replication and cause genomic instability. Abnormal R-loop accumulation can lead to DNA damage, cell cycle arrest, and cell death. Factors that resolve R-loops are essential for maintaining genomic stability and preventing disease. These factors include RNase H, helicases, topoisomerases, and DNA repair proteins. The resolution of R-loops varies throughout the cell cycle, with different factors acting at different stages. For example, the THO complex and Sen1 helicase are involved in resolving R-loops during the G1 and S phases, while RNase H2 is the primary factor during the G2/M phase. R-loop-related diseases include neurological disorders, cancers, and autoimmune conditions. Mutations in R-loop resolution factors can lead to the accumulation of R-loops, contributing to genomic instability and disease. Understanding the role of R-loops in the cell cycle and the factors that regulate their resolution is crucial for developing therapeutic strategies for diseases associated with R-loop dysregulation.The cell cycle is a crucial biological process that ensures the accurate replication and division of cells. It consists of G1, S, G2, and M phases, with the S phase being the DNA synthesis phase and the M phase involving mitosis. R-loops, which are three-stranded structures formed during transcription, can interfere with DNA replication and cause genomic instability. Abnormal R-loop accumulation can lead to DNA damage, cell cycle arrest, and cell death. Factors that resolve R-loops are essential for maintaining genomic stability and preventing disease. These factors include RNase H, helicases, topoisomerases, and DNA repair proteins. The resolution of R-loops varies throughout the cell cycle, with different factors acting at different stages. For example, the THO complex and Sen1 helicase are involved in resolving R-loops during the G1 and S phases, while RNase H2 is the primary factor during the G2/M phase. R-loop-related diseases include neurological disorders, cancers, and autoimmune conditions. Mutations in R-loop resolution factors can lead to the accumulation of R-loops, contributing to genomic instability and disease. Understanding the role of R-loops in the cell cycle and the factors that regulate their resolution is crucial for developing therapeutic strategies for diseases associated with R-loop dysregulation.