G-quadruplex–forming promoter sequences enable transcriptional activation in response to oxidative stress

Oxidative DNA damage is an implacable consequence of aerobic metabolism and often exacerbated in inflammatory processes that use reactive oxygen species (ROS) both as signaling molecules and as chemical warfare against pathogens. An extensive body of work, recently reviewed in ref. 1, has highlighted the deleterious consequences of oxidative DNA damage, which involves oxidized nucleobases that, if left unrepaired, are either mutagenic or strong replication blockers. Most oxidative DNA damage is efficiently processed by DNA repair pathways, primarily base excision repair (BER), the molecular details of which are generally well understood (2). However, an emerging area of research posits that certain oxidative DNA lesions and their associated repair complexes are intermediates in a signaling transduction cascade that uses ROS as secondary messengers to ultimately effect transcriptional regulation (3⇓⇓⇓–7). In PNAS, Fleming et al. (8) reinforce these notions by describing a compelling mechanism by which 8-oxoguanine (OG), a canonical oxidative DNA damage product, when occurring in guanine-rich, G-quadruplex–forming promoter sequences, directly up-regulates transcription of the downstream gene

Az uralkodó, a Szentszék és a magyar főpapok Luxemburgi Zsigmond korában

Th e Monarch, the Holy See and the Hungarian Prelates in the Era of Sigismund of Luxemburg. During the reign of Sigismund of Luxemburg (1387–1437), altogether 14 dioceses (two archiepiscopacies and 12 episcopates) functioned except for Croatia, which belonged to the Hungarian crown as well. Related to the church, Sigismund of Luxemburg made attempts to establish a personnel policy which was independent from the papacy. In 1404, he launched Placetum Regium. (According to this decree, Papal bulls could not be pronounced in Hungary without the consent of the king.) This reinforced the regulations of the national assembly held in 1397. Furthermore, the royal forbad to make the papal grantor bulls (provisio), citation letters as well as the judgements passed by the papal court public without his approval. In 1417, he have the cardinals participating in the Council of Constance acknowledged the right of patronage (ius supremi patronatus) of the Hungarian king. These things indicated that Sigismund and his successors had a possibility to fill in all the church benefices in the territory of the Hungarian Kingdom. During the reign of Sigismund, altogether 59 people received the pontificate in the country. This present study makes attempts to give a complex picture about the small group heading the Hungarian church hierarchy from different aspects, e.g. on the bases of their social origins, education, church and secular career, network system

Role of tautomerism in RNA biochemistry

Heterocyclic nucleic acid bases and their analogs can adopt multiple tautomeric forms due to the presence of multiple solvent-exchangeable protons. In DNA, spontaneous formation of minor tautomers has been speculated to contribute to mutagenic mispairings during DNA replication, whereas in RNA, minor tautomeric forms have been proposed to enhance the structural and functional diversity of RNA enzymes and aptamers. This review summarizes the role of tautomerism in RNA biochemistry, specifically focusing on the role of tautomerism in catalysis of small self-cleaving ribozymes and recognition of ligand analogs by riboswitches. Considering that the presence of multiple tautomers of nucleic acid bases is a rare occurrence, and that tautomers typically interconvert on a fast time scale, methods for studying rapid tautomerism in the context of nucleic acids under biologically relevant aqueous conditions are also discussed.National Institutes of Health (U.S.) (Grant P01 CA26731)National Institutes of Health (U.S.) (Grant R37 CA080024)National Institutes of Health (U.S.) (Grant P30 ES002109)National Institutes of Health (U.S.) (Training Grant T32 ES007020