The article discusses the role of R-loops in the cell cycle and their implications in diseases. R-loops are three-stranded nucleic acid structures consisting of an RNA:DNA hybrid and a single-stranded DNA. They are formed during transcription and can have both physiological and pathological roles. While R-loops are involved in various physiological processes, their aberrant accumulation can lead to DNA damage, genomic instability, and cell cycle arrest. The cell cycle, consisting of G1, S, G2, and M phases, is tightly regulated to ensure accurate replication and division of genetic material. R-loops can form during transcription and replication conflicts, particularly in the S phase, where transcription and replication share the same DNA template. This can lead to transcription-replication conflicts (TRCs), which can be head-on (HO) or co-directional (CD), with HO conflicts being more detrimental. The article highlights the importance of factors that resolve R-loops at different stages of the cell cycle, such as RNase H, helicases, topoisomerases, and other RNA processing factors. Defects in these factors can lead to R-loop accumulation, contributing to diseases such as neurological disorders and cancers. The article also emphasizes the need for further research to understand the complex interplay between R-loops, the cell cycle, and disease mechanisms.The article discusses the role of R-loops in the cell cycle and their implications in diseases. R-loops are three-stranded nucleic acid structures consisting of an RNA:DNA hybrid and a single-stranded DNA. They are formed during transcription and can have both physiological and pathological roles. While R-loops are involved in various physiological processes, their aberrant accumulation can lead to DNA damage, genomic instability, and cell cycle arrest. The cell cycle, consisting of G1, S, G2, and M phases, is tightly regulated to ensure accurate replication and division of genetic material. R-loops can form during transcription and replication conflicts, particularly in the S phase, where transcription and replication share the same DNA template. This can lead to transcription-replication conflicts (TRCs), which can be head-on (HO) or co-directional (CD), with HO conflicts being more detrimental. The article highlights the importance of factors that resolve R-loops at different stages of the cell cycle, such as RNase H, helicases, topoisomerases, and other RNA processing factors. Defects in these factors can lead to R-loop accumulation, contributing to diseases such as neurological disorders and cancers. The article also emphasizes the need for further research to understand the complex interplay between R-loops, the cell cycle, and disease mechanisms.