Extended Data Fig. 10: Related to Fig. 3. Further characterization of late-replicating TA-rich DSB sites.
From: Comprehensive interrogation of synthetic lethality in the DNA damage response
a, A Venn diagram showing the intersection between the 72 break sites and the 125 common fragile sites in the humCFS database. b, Example screenshot of MAST output from the 72 break sites. The most common motifs are shown in dark and light gray. Peak sequences contain multiple copies of the respective motifs. c, Plot showing the AT fraction per 20 base pair adjacent windows across 72 MRE11 ChIP-Seq peaks only found in the SMARCAL1 KO:sgFANCM cells. Peaks were aligned according to their peak center. The AT fraction was calculated per 20 base pair in a 1 kb window. Blackline indicates the mean and blue area indicates standard deviation. The average AT fraction of the human genome is shown as a grey dashed line. d, Boxplot showing the lengths (1-99 percentile) of all annotated TA repeats in the hg19 reference genome, grouped according to whether or not they overlap an MRE11 ChIP-Seq peak exclusively detected in SMARCAL1 KO:sgFANCM cells. The lower and upper ends of the boxplot indicate the 25th and 75th percentile values. Centre line represents median. 69/72 MRE11 peaks overlapped an annotated TA repeat. 66,575 annotated TA repeats do not overlap MRE11 peaks. The locations and lengths of (TA)n repeats in the hg19 reference genome were taken from van Wietmarschen et al., 2020. e, Heatmap showing percentage-normalized signal from Repli-seq data in GM06990 cells across 72 MRE11 ChIP-Seq peaks only found in the SMARCAL1 KO:sgFANCM cells. The average signal for each phase was taken per peak and ordered from late to early replication timing. f Pie chart showing 72 MRE11 ChIP-Seq peaks only found in the SMARCAL1 KO:sgFANCM cells categorized into replication timing phases based on the maximum signal below each peak using percentage-normalized signal tracks from Repli-seq data in GM06990 cells.
