Fig. 4: FANCM:SMARCAL1-deficient cells accumulate cruciforms that are predominantly cleaved by ERCC1–ERCC4.
From: Comprehensive interrogation of synthetic lethality in the DNA damage response
a, Representative cruciform, FANCM and SMARCAL1 ChIP–seq (n = 1) tracks spanning a 10-kb window on chromosome 3. b, Profile plots and heat maps showing the intensity of cruciform signal at sites where FANCM is enriched in SMARCAL1 KO cells and sites where SMARCAL1 is enriched in FANCM KO cells. c, Top, schematic representation of the cruciform unfolding assay on a model TA repeat substrate. Bottom, unfolding of TA-cruciform DNA by SMARCAL1, SMARCAL1 ΔRBM and FANCM (data are representative of three experimental replicates). The presence of the cruciform secondary structure was estimated by DNA cutting with EcoRI, which does not cut hairpins at cruciform DNA but cuts double-stranded DNA. d, Representative MRE11 ChIP–seq (n = 1) tracks from SMARCAL1 KO:sgFANCM cells that also have knockdown of one of the indicated nucleases. e, Quantification of MRE11 enrichment at 35 sites in FANCM:SMARCAL1-deficient cells that also have knockdown of one of the indicated nucleases (n = 1; error bars represent mean ± s.d.). f, A model depicting the compensating activities of FANCM and SMARCAL1 in maintaining genome stability at TA repeats. Complementary action of FANCM and SMARCAL1 directly unfolds cruciforms that form at TA-rich repeats. When both SMARCAL1 and FANCM are absent, cruciforms are cleaved by ERCC1–ERCC4, leading to DSB formation upon entry into mitosis.
