Nevertheless, cancer cells can be killed indirectly through synthetic lethality between the cancer drivers and their synthetic lethal partners, as has been demonstrated using the PARP inhibitor olaparib to eliminate breast cancer early onset (BRCA -mutant ovarian and BRCA -mutantr cells [ 165, 171, 172].
(C) Synthetic lethality between sod1∆ and pri2(C434A) mutant alleles.
Importantly, two different promoters were used to drive cardiomyocyte-specific Cre recombinase expression; however, similar results were observed between the two lines including a decrease in cardiomyocyte proliferation, a decrease in pro-growth and proliferative gene expression (the former via Wnt/β-catenin and the latter via TEAD), and embryonic lethality between E10.5-12.5.
The deletion of the gene Klf2 results in embryonic lethality between E12.5 and E14.5 due to circulatory defects [48].
Over-expression of Spry1 in Tie2-Cre expressing cells results in embryonic lethality between E10.5 to E11.
However, synthetic lethality between nhp2ins9 and rps15-1 appear to be due to a wider impairment of the H/ACA snoRNP function.
Disruption of Flk1 results in embryonic lethality between E8.5 to E9.5 with an absence of blood islands at E7.5 and no organized blood vessels in vivo [13].
A genetic screen identified the cohesin subunit Mcd1/Scc1 and its loader Scc2 as suppressors of the synthetic lethality between elg1 and ctf4.
Using a gene targeting strategy to ablate Pten gene function in the mouse causes embryonic lethality between days 6.5 to 9.5 of gestation [8], [9], [10], [11].
In this respect, we tried to identify specific synthetic lethality between rps15-1 and a subset of H-ACA snoRNA guides targeted close to the binding site of Rps15p on 18S rRNA, driven by snrR36 and snR85.
To get a more quantifiable analysis of embryonic lethality between 5.5 and 7.5 dpc, we repeated the above mentioned experiment starting with homozygous instead of heterozygous GFP-TIAR α and β males.
