Likewise, CRISPR/Cas9-based targeted knockout of RTEL1 lead to a marked increase in R-loop accumulation, an effect that was also reversed in cells overexpressing RNase H (Fig. 4C,D; Supplemental Fig. S3E), Notably, elevated R-loops were also detected in RTEL1-depleted normal human diploid cells RPE-1 (Supplemental Fig. S3F), thereby excluding the possibility that the R-loop-antagonizing function of RTEL1 is restricted to cancer cells. Here, RTEL1 is linked to cancer.