Figure 4. Inheritable mutagenic G-quadruplexes during organogenesis.

(a) Schematic diagram of G4 instability reporter pLM88 and two categorically different TMEJ-generated repair outcomes. Although deletions <100 bp in size will retain the NLS in the LacZ ORF, deletions >100 bp will remove the NLS from the LacZ ORF. (b) Quantification of stochastic pLM88 ORF correction in asynchronous populations of the indicated genotype. Average percentage of LacZ-positive animals (n>180) of three independent experiments is depicted and error bars represent s.e.m. (c) Quantification of LacZ patterns in synchronized populations of dog-1-deficient animals transgenic for the G4 instability reporter (as illustrated in d). Average percentage of LacZ-positive animals of three independent experiments is depicted and error bars represent s.e.m. (d) Representative pictures of stochastic LacZ expression patterns of dog-1-deficient animals transgenic for the G4 instability reporter. Scale bar, 0.1 mm. (e) Comparison of the observed frequency of double events (as illustrated in d, right panels) and the expected frequency of such double staining patterns based on the frequency of the individual nuclear/cytoplasmic LacZ patterns. Asterisk indicates highly significant (P<0.001) overrepresentation of double events within the population (n=1,933) as determined by hypergeometric testing.