Yeast THO null mutants are sick and slow growers and THO depletion has a negative effect on growth rate of human and Drosophila cell lines [ 6, 7, 12].
hns mutants are exceptionally sick, accumulate suppressors rapidly, and are cold-sensitive (i.e., the grow poorly at 20°C; Dersch et al., 1994 MGG 2452555).
Interestingly, Top2 and Hmo1 physically interact with Yra1 (Ho et al., 2002; Krogan et al., 2006), and top2 mutants are synthetic sick with HPR1 or SAC3 mutations (data not shown) (Aguilera and Klein, 1990).
Because strong unc-112 mutants are very sick and develop extremely slowly, we performed our unc-112 epistatic studies in a dim-1 mutant background that suppresses the developmental delay of unc-112 mutants but has no visible effect by itself on engulfment (Table 1).
elg1 Δ srs2 Δ double mutants are extremely sick as haploids (Parnas et al. 2010), indicating that cells need at least one of the proteins to carry out a function important for fitness, probably some type of repair that is so common that it occurs often during DNA replication, such as fork stalling response.
It is interesting to note that elg1 mutants are synthetic sick with mutations in HTB1 (data not shown), RTT106 (Imbeault et al. 2008), RTT109 (Bellaoui et al. 2003), although not with chd1 Δ, nhp6a Δ or the double nhp6a Δ nhp6b Δ (data not shown).
Mutants lacking homologous recombination proteins often are sicker in h − than in h + configuration, which is presumed to reflect the absence of a template for repair of the mating type imprint and break required for switching in the h− strain (Khasanov et al. 1999).
Pharyngeal pumping was similarly unaffected in either allele at 6-days of age (Supplementary Material, Fig. S5), indicating that dnj-14 mutants are neither generally sick nor defective in functions of the worm head region.
The pioneering study by Willingham et al. (21) used the yeast collection of 4852 haploid mutants containing deletions of non-essential genes to identify those mutants that were sick or synthetically lethal with WT α-syn.
In the high-throughput screening format, esl1 Δ was synthetic sick with four other deletions, esl2 Δ was sick or lethal with 12 other deletions, and esl1 Δ esl2 Δ double mutants were synthetic sick or lethal with another seven gene deletions (Table 2).
