Wagner Jennifer K, Marquis Kathleen A, Rudner David Z
Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115, USA.
Mol Microbiol. 2009 Sep;73(5):963-74. doi: 10.1111/j.1365-2958.2009.06825.x. Epub 2009 Aug 4.
How cells maintain their ploidy is relevant to cellular development and disease. Here, we investigate the mechanism by which the bacterium Bacillus subtilis enforces diploidy as it differentiates into a dormant spore. We demonstrate that a sporulation-induced protein SirA (originally annotated YneE) blocks new rounds of replication by targeting the highly conserved replication initiation factor DnaA. We show that SirA interacts with DnaA and displaces it from the replication origin. As a result, expression of SirA during growth rapidly blocks replication and causes cell death in a DnaA-dependent manner. Finally, cells lacking SirA over-replicate during sporulation. These results support a model in which induction of SirA enforces diploidy by inhibiting replication initiation as B. subtilis cells develop into spores.
细胞如何维持其倍性与细胞发育和疾病相关。在此,我们研究了枯草芽孢杆菌在分化为休眠孢子时维持二倍体状态的机制。我们证明,一种孢子形成诱导蛋白SirA(最初注释为YneE)通过靶向高度保守的复制起始因子DnaA来阻止新一轮的复制。我们表明,SirA与DnaA相互作用并将其从复制起点上置换下来。结果,生长过程中SirA的表达迅速阻断复制,并以依赖DnaA的方式导致细胞死亡。最后,缺乏SirA的细胞在孢子形成过程中过度复制。这些结果支持了一个模型,即随着枯草芽孢杆菌细胞发育成孢子,SirA的诱导通过抑制复制起始来维持二倍体状态。