Somatic mutations in DNA‐binding sites for CCCTC‐binding factor (CTCF) are significantly elevated in many cancers. Prior analysis has suggested that elevated mutation rates at CTCF‐binding sites in skin cancers are a consequence of the CTCF‐cohesin complex inhibiting repair of UV damage. Here, we show that CTCF binding modulates the formation of UV damage to induce mutation hot spots. Analysis of genome‐wide CPD‐seq data in UV‐irradiated human cells indicates that formation of UV‐induced cyclobutane pyrimidine dimers (CPDs) is primarily suppressed by CTCF binding but elevated at specific locations within the CTCF motif. Locations of CPD hot spots in the CTCF‐binding motif coincide with mutation hot spots in melanoma. A similar pattern of damage formation is observed at CTCF‐binding sites in vitro, indicating that UV damage modulation is a direct consequence of CTCF binding. We show that CTCF interacts with binding sites containing UV damage and inhibits repair by a model repair enzyme in vitro. Structural analysis and molecular dynamic simulations reveal the molecular mechanism for how CTCF binding modulates CPD formation.
Double-stranded (ds) Invader and INA probes allow for efficient and specific recognition of mixed-sequence dsDNA targets, whereas recognition is less efficient and specific with single-stranded LNA-modified DNA strands and fully modified MPγPNAs.
Chimeric γPNA–Invader probes are energetically activated to recognize complementary double-stranded (ds) DNA targets and engineered to reduce γPNA dimerization and improve the specificity of the recognition process vis-à-vis single-stranded γPNAs.
Three probe chemistries are evaluated with respect to thermal denaturation temperatures, UV-Vis and fluorescence characteristics, recognition of complementary and mismatched DNA hairpin targets, and recognition of chromosomal DNA targets in...
Invader probes featuring non-nucleotidic bulges are energetically activated for highly specific recognition of complementary double-stranded DNA targets.
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