The polarity proteins PAR-4 and PAR-1 delay cell division in early C. elegans embryos by inhibiting DNA replication, Benkemoun et al. reveal.
Cells must divide at the right time during development. This is true from the get-go in C. elegans embryos where, at the two-cell stage, the anterior blastomere divides while its smaller, posterior sister is still in S phase. This cell cycle asynchrony is promoted by proteins that regulate embryonic polarity, such as the kinases PAR-4 and PAR-1. In embryos lacking these proteins, the posterior blastomere speeds through S phase so that both cells divide at the same time. But how PAR-4 (a homologue of human LKB1) regulates the cell cycle is unclear.
By imaging the replication protein PCN-1, the C. elegans orthologue of PCNA, Benkemoun et al. found that the posterior blastomere in wild-type embryos took longer to complete S phase than the anterior cell because, at every time point, it contained fewer sites of active DNA replication. But in the absence of PAR-4, or its downstream target PAR-1, the posterior blastomere formed just as many replication foci as its anterior sister. Knocking down proteins that initiate DNA replication increased the duration of S phase in the posterior blastomere of PAR-4–deficient embryos, restoring division asynchrony and enhancing embryonic viability.
Senior author Jean-Claude Labbé now wants to investigate how PAR-4 and PAR-1 inhibit replication initiation in the posterior blastomere.
Text by Ben Short