Clovis Y et al. (2016) MicroPubl Biol "Mutations in KCNQ potassium channels cause pharyngeal pumping defects in C. elegans."

Turner C, Webb A, Clovis Y, Roberts B

[MicroPubl Biol, 2016]

Pumps were stimulated with 10mM 5HT in M9 recorded as electropharyngeograms (EPGs) for 2 minutes in a NemaMetrix ScreenChip, and analyzed using NemAnalysis software (NemaMetrix). The null mutant strains kqt-1(aw3) and kqt-3 (aw1) were kindly donated by Dr. Aguan Wei (Wei et al., 2002) A) Pump frequency in kqt-1(aw3) animals was significantly lower than in N2s, while kqt-3(aw1) worms showed an increase in pump frequency (*p<0.05; ***p<0.01; 1-tailed Mann-Whitney U-test; n = 21-23 worms in each strain). B) Microfluidic EPG recordings show that pumping pattern in kqt-1(aw3) mutants is arrhythmic, with frequent drops in frequency. C) Overlay of first 50 pumps of recordings show that pump duration is higher in kqt-1(aw3) and kqt-3(aw1) animals than in N2s. Pumps are showed aligned on E spikes, which occur when the pharynx is fully contracted. D) Duration histogram illustrating the probability of occurrence of inter-pump interval (E to E duration) for each mutant strain. Histograms were binned to 4 ms width and normalized to reach an area underneath the curve equal to 1 (duration 100% likelihood to occur). In kqt-1(aw3)) animals, the time between two pumps is significantly increased compared to N2s (p < 0.01).

Kim SH et al. (2007) J Cell Biol "SMK-1/PPH-4.1-mediated silencing of the CHK-1 response to DNA damage in early C. elegans embryos."

Wolff S, Holway AH, Michael WM, Kim SH, Dillin A

[J Cell Biol, 2007]

During early embryogenesis in Caenorhabditis elegans, the ATL-1-CHK-1 (ataxia telangiectasia mutated and Rad3 related-Chk1) checkpoint controls the timing of cell division in the future germ line, or P lineage, of the animal. Activation of the CHK-1 pathway by its canonical stimulus DNA damage is actively suppressed in early embryos so that P lineage cell divisions may occur on schedule. We recently found that the rad-2 mutation alleviates this checkpoint silent DNA damage response and, by doing so, causes damage-dependent delays in early embryonic cell cycle progression and subsequent lethality. In this study, we report that mutations in the smk-1 gene cause the rad-2 phenotype. SMK-1 is a regulatory subunit of the PPH-4.1 (protein phosphatase 4) protein phosphatase, and we show that SMK-1 recruits PPH-4.1 to replicating chromatin, where it silences the CHK-1 response to DNA damage. These results identify the SMK-1-PPH-4.1 complex as a critical regulator of the CHK-1 pathway in a developmentally relevant context.