TASK DEFINITION: Given a context passage, generate a question from the passage such that its answer is shortest continous span from the passage.
PROBLEM: Specific outcomes upon activation of the c-Jun N-terminal kinase (JNK) pathway critically depend on the intensity and duration of signal transmission. Dual-specificity phosphatases (DUSPs) play a very important role in these events by modulating the extent of JNK phosphorylation and activation and thus regulating cellular responses to stress. M3/6 (DUSP8) is one of the dual-specificity protein phosphatases with distinct specificity towards JNK. It has been shown that M3/6 itself is phosphorylated by JNK upon stimulation with arsenite, but the role of this phosphorylation has not been investigated. In this study, we mapped JNK-induced phosphorylation sites on M3/6 using mass spectrometry. Phosphorylated residues Ser 515, Thr 518 and Ser 520 were identified and site-directed mutagenesis was employed to investigate their role. Upon arsenite stimulation, M3/6 mutated at these sites exhibited decreased phosphorylation compared to the wild-type protein. No difference was observed in terms of the enzyme's in vitro phosphatase activity, its substrate specificity towards JNK isoforms, its interactions with JNK and the scaffold family of JNK-interacting proteins (JIPs), its stability or its subcellular localization. Interestingly, expression of M3/6 phosphorylation mutants delayed the time-course of JNK phosphorylation and activation by arsenite. We propose that phosphorylation of the M3/6 phosphatase by JNK in response to stress stimuli results in attenuation of phosphatase activity and acceleration of JNK activation.

SOLUTION: Which protein is affected by dusp8 activation?

PROBLEM: It has been previously shown that disruption of RAD26 in yeast strain W303-1B results in a strain that is deficient in transcription-coupled repair (TCR), the preferential repair of the transcribed strand of an expressed gene over the non-transcribed strand and the rest of the genome. RAD26 encodes a protein that is homologous to Cockayne syndrome group B protein (CSB) and is a member of the SWI2/SNF2 family of DNA-dependent ATPases involved in chromatin remodeling. Like the rad26 mutant, cells from Cockayne syndrome patients are defective in TCR. We examined the role of Rad26 in TCR by disrupting RAD26 in two repair-proficient laboratory strains and, remarkably, observed no effect upon TCR. Our results indicate that disruption of RAD26 alone is insufficient to impair TCR. Thus, W303-1B must already possess a mutation that, together with disruption of RAD26, causes a deficiency in TCR. We suggest that other genes are mutated in Cockayne syndrome cells that contribute to the deficiency in TCR. Surprisingly, deletion of RAD26 results in expression of genes that are repressed by flanking transposon delta elements, an Spt(-) phenotype. The delta elements appear to perturb local chromatin structure. Expression of genes flanked by delta elements in rad26Delta mutants is consistent with a role for Rad26 in chromatin remodeling.

SOLUTION: Which gene strand is targeted by transcription-coupled repair (TCR)?

PROBLEM: The Narym River is a river in the Eastern Kazakhstan, a tributary of the Irtysh River, originating at the junction of the ridges Narym and Sarymsakty of wetland formed by the mountain runoff streams.

SOLUTION:
The body of water that Narym River is near is what?