The 14-3-3 genepar-5is required for germline development and DNA damage response inCaenorhabditis elegans.

Abstract

14-3-3 proteins have been extensively studied from yeast to mammals and associated with multiple roles ranging from fundamental processes such as cell cycle, apoptosis and stress response to diseases such as cancer. In Caenorhabditis elegans, there are two 14-3-3 genes, ftt-2 and par-5. The ftt-2 gene is expressed only in somatic lineages, whereas par-5 expression is detected in both soma and germline. In early embryonic development, par-5 is necessary to establish cell polarity. Although it is known that par-5 inactivation results in sterility, the role of this gene in germline development is poorly characterized. In the present study, we use a par-5 mutation and RNA interference to characterize par-5 functions in the germline. The lack of par-5 in germ cells causes cell cycle deregulation, the accumulation of endogenous DNA damage and genomic instability. Moreover, par-5 is required for checkpoint-induced cell cycle arrest in response to DNA-damaging agents. We propose a model where PAR-5 regulates CDK-1 phosphorylation to prevent premature mitotic entry. This study opens a new path to investigate the mechanisms of 14-3-3 functions, which are not only essential for worm development but also have been shown altered in human diseases.