ATM in focus:a damage sensor and cancer target

The ability of a cell to conserve and maintain its native DNA sequence is fundamental for the survival and normal functioning of the whole organism and protection from cancer development. Here we review recently obtained results and current topics concerning the role of the ataxia-telangiectasia mutated (ATM) protein kinase as a damage sensor and its potential as therapeutic target for treating cancer. This monograph discusses DNA repair mechanisms activated after DNA double-strand breaks (DSBs), i.e. non-homologous end joining, homologous recombination and single strand annealing and the role of ATM in the above types of repair. In addition to DNA repair, ATM participates in a diverse set of physiological processes involving metabolic regulation, oxidative stress, transcriptional modulation, protein degradation and cell proliferation. Full understanding of the complexity of ATM functions and the design of therapeutics that modulate its activity to combat diseases such as cancer necessitates parallel theoretical and experimental efforts. This could be best addressed by employing a systems biology approach, involving mathematical modelling of cell signalling pathways

A novel lncRNA as a positive regulator of carotenoid biosynthesis in Fusarium

The fungi Fusarium oxysporum and Fusarium fujikuroi produce carotenoids, lipophilic terpenoid pigments of biotechnological interest, with xanthophyll neurosporaxanthin as the main end product. Their carotenoid biosynthesis is activated by light and negatively regulated by the RING-finger protein CarS. Global transcriptomic analysis identified in both species a putative 1-kb lncRNA that we call carP, referred to as Fo-carP and Ff-carP in each species, upstream to the gene carS and transcribed from the same DNA strand. Fo-carP and Ff-carP are poorly transcribed, but their RNA levels increase in carS mutants. The deletion of Fo-carP or Ff-carP in the respective species results in albino phenotypes, with strong reductions in mRNA levels of structural genes for carotenoid biosynthesis and higher mRNA content of the carS gene, which could explain the low accumulation of carotenoids. Upon alignment, Fo-carP and Ff-carP show 75-80% identity, with short insertions or deletions resulting in a lack of coincident ORFs. Moreover, none of the ORFs found in their sequences have indications of possible coding functions. We conclude that Fo-carP and Ff-carP are regulatory lncRNAs necessary for the active expression of the carotenoid genes in Fusarium through an unknown molecular mechanism, probably related to the control of carS function or expressio

Comparative Analysis of Tick-Borne Relapsing Fever Spirochaetes from Ethiopia and Nigeria

Despite increasing reports of tick-borne diseases in Africa, remarkably, reports of tick-borne relapsing fever (TBRF) in Nigeria are lacking. Ornithodoros savignyi from Nigeria have been reported with the relapsing fever Candidatus Borrelia kalaharica. Conversely, in Ethiopia, the agent of relapsing fever is the louse-borne relapsing fever (LBRF) spirochaete Borrelia recurrentis with no TBRF reported to occur. A total of 389 Ornithodoros ticks, Ethiopia (N = 312) and Nigeria (N = 77), were sampled, together with 350 cattle, and 200 goat sera were collected from Nigeria. Samples were screened for Borrelia spp. by RT-PCR. Reactive samples were confirmed, then sequenced using flagellin B, 16S rRNA, and 16S–23S intergenic spacer region. The prevalence of Borrelia spp. in livestock was 3.8% (21/550) and 14% (3/21) after final molecular confirmation. Of 312 ticks from Ethiopia, 3.5% (11/312) were positive for Borrelia, with 36% (4/11) by conventional PCR. Sequencing revealed that the borreliae in soft ticks was C. B. kalaharica, whilst that found in animals was Borrelia theileri. Soft ticks were confirmed by sequencing 7% (22/312) and 12% (9/77) of the Ethiopian and Nigerian ticks, respectively. Phylogenetic analysis revealed that these were Ornithodoros savignyi. This is the first evidence of C. B. kalaharica in Ethiopia and demonstrates the co-existence of TBRF in a country endemic to LBRF. Important, this might cause a diagnostic challenge given that LBRF is predominantly diagnosed by microscopy, which cannot differentiate these two spirochaetes. Furthermore, we report B. theileri in ruminants in Nigeria, which may also be of veterinary and economic importance

Congruence of chloroplast- and nuclear-encoded DNA sequence variations used to assess species boundaries in the soil microalga Heterococcus (Stramenopiles, Xanthophyceae).

BackgroundHeterococcus is a microalgal genus of Xanthophyceae (Stramenopiles) that is common and widespread in soils, especially from cold regions. Species are characterized by extensively branched filaments produced when grown on agarized culture medium. Despite the large number of species described exclusively using light microscopic morphology, the assessment of species diversity is hampered by extensive morphological plasticity.ResultsTwo independent types of molecular data, the chloroplast-encoded psbA/rbcL spacer complemented by rbcL gene and the internal transcribed spacer 2 of the nuclear rDNA cistron (ITS2), congruently recovered a robust phylogenetic structure. With ITS2 considerable sequence and secondary structure divergence existed among the eight species, but a combined sequence and secondary structure phylogenetic analysis confined to helix II of ITS2 corroborated relationships as inferred from the rbcL gene phylogeny. Intra-genomic divergence of ITS2 sequences was revealed in many strains. The 'monophyletic species concept', appropriate for microalgae without known sexual reproduction, revealed eight different species. Species boundaries established using the molecular-based monophyletic species concept were more conservative than the traditional morphological species concept. Within a species, almost identical chloroplast marker sequences (genotypes) were repeatedly recovered from strains of different origins. At least two species had widespread geographical distributions; however, within a given species, genotypes recovered from Antarctic strains were distinct from those in temperate habitats. Furthermore, the sequence diversity may correspond to adaptation to different types of habitats or climates.ConclusionsWe established a method and a reference data base for the unambiguous identification of species of the common soil microalgal genus Heterococcus which uses DNA sequence variation in markers from plastid and nuclear genomes. The molecular data were more reliable and more conservative than morphological data