chk-1 is an essential gene and is required for an S-M checkpoint during early embryogenesis.

The chk1 gene was first discovered in screens for radiation sensitive mutants in S. pombe.(1) Genetic analysis revealed that chk1 is involved in a DNA damage G(2)-M checkpoint. Chk1 becomes activated in response to DNA damage and prevents entry into mitosis by inhibiting the cell cycle machinery. This checkpoint decreases the risk of defective DNA being inherited by daughter cells, therefore reducing the risk of genetic instability. In higher eukaryotes, chk1 homologues have similar checkpoint functions. For example, an avian B-lymphoma cell line that is defective for Chk1 fails to arrest in G(2)-M after DNA damage. Nonetheless, these Chk1 defective cells are viable indicating that Chk1 is not essential for normal somatic cells to divide.(2) In spite of this, mouse and Drosophila homozygous Chk1 mutants die during embryogenesis suggesting that this is an essential gene for embryonic cell cycles.(3,4) What particular role does Chk1 have in directing embryonic cell divisions? Here we used the model organism, C. elegans, to address the role of chk-1 during development. As expected, disruption of chk-1 by RNAi eliminated the DNA damage checkpoint response in C. elegans. In addition, we revealed that chk-1 was predominantly expressed during embryogenesis and in the postembryonic germline. Indeed, we found that chk-1 had an essential role in embryo and germline development. More specifically, disruption of chk-1 expression resulted in embryo lethality, which was attributed to a defect in an intrinsic S-M checkpoint hence causing premature entry into M-phase.

Whole-genome analysis of 60 G protein-coupled receptors in Caenorhabditis elegans by gene knockout with RNAi.

G protein-coupled receptors (GPCRs) are the largest family of genes in animal genomes and represent more than 2% of genes in humans and C. elegans. These evolutionarily conserved seven-transmembrane proteins transduce a diverse range of signals. In view of their pivotal role in cell signaling, it is perhaps surprising that decades of genetic analysis in C. elegans, and recent genome-wide RNAi screens, have identified very few GPCR mutants. Therefore, we screened all GPCRs predicted to bind either small-molecule neurotransmitters or neuropeptides by using RNAi and quantitative behavioral assays. This shows that C16D6.2, C25G6.5, C26F1.6, F35G8.1, F41E7.3, and F59C12.2 are likely to be involved in reproduction, whereas C15B12.5, C10C6.2, C24A8.4, F15A8.5, F59D12.1, T02E9.1, and T05A1.1 have a role in locomotion. Gene deletions for F35G8.1 and T05A1.1 resulted in the same phenotype as that seen with RNAi. As some GPCRs may be resistant to RNAi, or may result in abnormalities not screened for here, the actual proportion of nonredundant receptors with an assayable function is probably greater. Strikingly, most phenotypes were observed for NPY-like receptors that may bind neuropeptides. This is consistent with the known actions of neuropeptides on the body wall muscle and reproductive tract in nematodes.