Given a context passage, generate a question from the passage such that its answer is shortest continous span from the passage.

[Q]: Lack of the yeast Rrm3p DNA helicase causes replication defects at multiple sites within ribosomal DNA (rDNA), including at the replication fork barrier (RFB). These defects were unaltered in rrm3 sir2 cells. When the RFB binding Fob1p was deleted, rrm3-generated defects at the RFB were eliminated, but defects at other rDNA sites were not affected. Thus, specific protein-DNA complexes make replication Rrm3p-dependent. Because rrm3-induced increases in recombination and cell cycle length were only partially suppressed in rrm3 fob1 cells, which still required checkpoint and fork restart activities for viability, non-RFB rrm3-induced defects contribute to rDNA fragility and genome instability.
[A]: What is the effect of the absence of Saccharomyces cerevisiae Rrm3p?


[Q]: In this phase 2 proof-of-concept study we examined the safety and efficacy of selexipag, an orally available, selective prostacyclin receptor (IP receptor) agonist, as a treatment for pulmonary arterial hypertension (PAH). 43 adult patients with symptomatic PAH (receiving stable endothelin receptor antagonist and/or a phosphodiesterase type-5 inhibitor therapy) were randomised three to one to receive either selexipag or placebo. Dosage was up-titrated in 200-g increments from 200 g twice daily on day 1 to the maximum tolerated dose by day 35 (maximum allowed dose of 800 g twice daily). Change in pulmonary vascular resistance at week 17 expressed as a percentage of the baseline value was the primary efficacy end-point, and was analysed in the per protocol set first and then in the all-treated set to assess robustness of results. A statistically significant 30.3% reduction in geometric mean pulmonary vascular resistance was observed after 17 weeks' treatment with selexipag compared with placebo (95% confidence limits -44.7- -12.2; p=0.0045, Wilcoxon rank sum test). This was supported by a similar result from the all-treated set. Selexipag was well tolerated with a safety profile in line with the expected pharmacological effect. Our results encourage the further investigation of selexipag for the treatment of PAH.
[A]: Selexipag is used for which disease?


[Q]: Nucleotide excision repair (NER) in eukaryotes is a pathway conserved from yeast to humans that removes many bulky chemical adducts and UV-induced photoproducts from DNA in a relatively error-free manner. In addition to the recognition and excision of DNA damage throughout the genome (GGR), there exists a mechanism, transcription-coupled nucleotide excision repair (TCR), for recognizing some types of DNA damage in the transcribed strand of genes in Escherichia coli, yeast and mammalian cells. An obstacle in the repair of the transcribed strand of active genes is the RNA polymerase complex stalled at sites of DNA damage. The stalled RNA polymerase complex may then mediate recruitment of repair proteins to damage in the transcribed strand. Proteins enabling TCR are the Cockayne syndrome B (CSB) protein in humans and its yeast homologue Rad26. Both CSB and Rad26 belong to the Swi2/Snf2 family of DNA-dependent ATPases, which change DNA accessibility to proteins by altering chromatin structure. To address how Rad26 functions in yeast repair, we used the genetic approach of overexpressing Rad26 and examined phenotypic changes, i.e. changes in NER. We found that repair of both the transcribed and the non-transcribed strands is increased. In addition, overexpression of Rad26 partially bypasses the requirement for Rad7 in GGR, specifically in the repair of non-transcribed sequences. As TCR takes place in very localized regions of DNA (i.e. within genes) in wild-type cells, we propose that overexpression of recombinant Rad26 increases accessibility of the damaged DNA in chromatin for interaction with repair proteins.
[A]:
Which gene strand is targeted by transcription-coupled repair (TCR)?