Insertional mutants of genes from both the Ribonuclease H and RNA-directed DNA polymerase activities gene families are virulence defectives (Table 2).
In aggregate, although no deviations from the normal pattern were observed in 96 wild-type segments examined, a quarter of the 228 mutant hemisegments contained defects and every importin-α2 mutant larva had at least 1 defective hemisegment (Table 1).
Six compounds were categorized as resistance due to the mismatch repair defective phenotype (Table S2).
Compounds that did not affect the lag phase in the mutator strain were categorized as resistance due to the mismatch repair defective phenotype (Table S2).
About 2.5% of the embryos showed EC defects (defective AV septum with defective valve development; Fig. 3I) (Table 4).
This class consists of seven mutants, all of which have defective vulval morphology (Table 8).
I'm not losing sleep over this episode — if I had felt that the table was defective, I would have fixed it.
Seven of these candidates were defective in heart development (Table 3), a significant increase over background (P = 0.0064, binomial distance).
Human patients with these mutations display severe neurological abnormalities, reduced growth, and delayed and defective development (supplementary material Table S1; Bergmann and Egly, 2001; Botta et al., 2002; Broughton et al., 1995; Viprakasit et al., 2001; Theron et al., 2005; Fujimoto et al., 2005).
To investigate this and to determine whether the effects of combining exonuclease-defective alleles of POL2 (Table 2) and POL3 (Table 4) with a polymerase active site defect were specific to Y831A Pol ε, we looked for genetic interaction between proofreading and mutator alleles of the POL1 (encoding Pol α) and the POL3 (encoding Pol δ).
The mutation rate in dnaE915 is ∼5-fold lower than the isogenic DnaE+ control, and this effect remains in the Lex-defective background (Figure 1G, Table 1).
