Fission yeast Rad26ATRIP delays spindle-pole-body separation following interphase microtubule damage

Abstract

The conserved fission yeast protein Rad26ATRIP preserves genomic stability by occupying central positions within DNA-structure checkpoint pathways. It is also required for proper cellular morphology, chromosome stability and following treatment with microtubule poisons. Here, we report that mutation of a putative nuclear export sequence in Rad26ATRIP disrupted its cytoplasmic localization in untreated cells and conferred abnormal cellular morphology, minichromosome instability and sensitivity to microtubule poisons without affecting DNA-structure checkpoint signaling. This mutation also disrupted a delay to spindle-pole-body separation that occurred following microtubule damage in G2. Together, these results demonstrate that Rad26ATRIP participates in two genetically defined checkpoint pathways – one that responds to genomic damage and the other to microtubule damage. This response to microtubule damage delays spindle-pole-body separation and, in doing so, might preserve both cellular morphology and chromosome stability.

Intercellular Delay Regulates the Collective Period of Repressively Coupled Gene Regulatory Oscillator Networks

“…We use co-repression to establish the intercellular signaling [12]. This is based on the facts that 1) mutual repression between a pair of biological oscillators constitutes a positive feedback loop coupling between the oscillators, which is regarded as the most prevalent induction scheme of synchronization in homogeneous biological oscillators [12]; and 2) intercellular repression is widespread in gene regulatory networks [22].…”

“…This is based on the facts that 1) mutual repression between a pair of biological oscillators constitutes a positive feedback loop coupling between the oscillators, which is regarded as the most prevalent induction scheme of synchronization in homogeneous biological oscillators [12]; and 2) intercellular repression is widespread in gene regulatory networks [22]. The i th oscillator's dynamics is described by: $$true\{\begin{array}{c}left\frac{d{m}_i\left(t\right)}{dt}=g(p_i(t-T_m),m_{{\mathrm{double-struckN}}_{\stackrel{‒}{i}}})(t-\tau )-c{m}_i\left(i\right),\\ left\frac{d{p}_i\left(t\right)}{dt}=a{m}_i(t-T_p)-b{p}_i\left(t\right),i=1,2,\dots ,N\end{array}\phantom{\}}$$ where $g(p_i\left(t\right),m_{{\mathbb{N}}_{\stackrel{false‒}{i}}}\left(t\right))=\frac{k}{1+1\frac{p_i^{\nu }\left(t\right)}{p_0^{\nu }}+{\sum }_{j\in {\mathbb{N}}_{\stackrel{false‒}{i}}}1\frac{m_j^{\nu }\left(t\right)}{m_0^{\nu }}}$ and ${\mathrm{double-struckN}}_{\stackrel{‒}{i}}$ denotes index set { j = 1, 2, .…”

“…In this case, by using the subnetwork replacement technique [23], the interaction cascade can be replaced with “ her 1 /her 7 mRNA in cell 1 ⊣ her 1 /her 7 mRNA in cell 2” without changing the qualitative characteristics of intercellular interaction [23]. Given this, (2) can be used to model many biochemical oscillator networks such as the insulin secreting pancreatic islets [12], ovulation regulation networks [12], and neural stem cell maintenance networks [24], to name a few.…”

“…Biological rhythms as diverse as cell-cycles in bacterial [9], segmentation clocks in vertebrates [10], and circadian rhythms in mammals [11] depend heavily on autorepression. Following the same principles, we model the intercellular interaction as co-repression based on the fact that mutual repression between a pair of oscillators comprises a positive feedback loop between the oscillators, which has been reported to synchronize various biological oscillators [12]. This model is also inspired by the fact that intercellular repression is widespread in sensory pyramidal neurons [13], visual thalamus [14], and insulin secretion [15], to name a few examples.…”

Polycyclic aromatic hydrocarbons and small related molecules: Effects on Schizosaccharomyces pombe morphology measured by imaging flow cytometry

“…One example is the Rad26 deletion (rad26) strain designated 1001, which does not produce the Rad26 protein. Rad26 serves to respond to structural abnormalities of DNA and the microtubule cytoskeleton (al-Khodairy, 1994;De Souza, 1999;Baschal, 2006;Herring, 2010).…”