The cartoons show the manipulation of the
BU-1A locus in which the +3.5 G4 motif has already been deleted from both the
BU-1A and
BU-1B allele. Only the first three exons are shown along with the sequence reintroduced in the position of the original +3.5 G4 motif. (i)
BU1A with the +3.5 kb G4 DNA deleted. (ii)
BU1A with the +3.5 kb G4 DNA reintroduced. (iii)
BU1A with the +3.5 kb G4 DNA reintroduced with two point mutations that abolish intramolecular G quadruplex formation
in vitro (Fig
3B). (iv)
BU1A with the +3.5 kb G4 DNA reintroduced inverted such that it would be present on the lagging strand template for a replication fork entering from the right of the locus. To the right is the fluctuation analysis of Bu-1a loss for each mutant. Each point represents the percentage of Bu-1a
low variants in clones expanded for 20 generations. Red bar = median loss; whiskers = interquartile range;
P-values that each distribution is different from control (i) calculated with Fisher's exact test with a bin size of 20%. NS = not significant (
P < 0.001).