Controlling the Synchronization of Molecular Oscillators through Indirect Coupling.

In this article, we study the coupling of a collection of molecular oscillators, called repressilators, interacting indirectly through enzymatic saturation. We extended a measure of autocorrelation to identify the period of the whole system and to detect coupling behaviors. We explored the parameter space of concentrations of molecular species in each oscillator versus enzymatic saturation, and observed regions of uncoupled, partially, or fully coupled systems. In particular, we found a region that provided a sharp transition between no coupling, two coupled oscillators, and full coupling. In practical applications, signals from the environment can directly affect parameters such as local enzymatic saturation, and thus switch the system from a coupled to an uncoupled regime and vice-versa. Our parameter exploration can be used to guide the design of complex molecular systems, such as active materials or molecular robot controllers.

SGO1 is involved in the DNA damage response in MYCN-amplified neuroblastoma cells.

Shugoshin 1 (SGO1) is required for accurate chromosome segregation during mitosis and meiosis; however, its other functions, especially at interphase, are not clearly understood. Here, we found that downregulation of SGO1 caused a synergistic phenotype in cells overexpressing MYCN. Downregulation of SGO1 impaired proliferation and induced DNA damage followed by a senescence-like phenotype only in MYCN-overexpressing neuroblastoma cells. In these cells, SGO1 knockdown induced DNA damage, even during interphase, and this effect was independent of cohesin. Furthermore, MYCN-promoted SGO1 transcription and SGO1 expression tended to be higher in MYCN- or MYC-overexpressing cancers. Together, these findings indicate that SGO1 plays a role in the DNA damage response in interphase. Therefore, we propose that SGO1 represents a potential molecular target for treatment of MYCN-amplified neuroblastoma.