Binding of mismatch repair protein MutS to mispaired DNA adducts of intercalating ruthenium(II) arene complexes

The present study was performed to examine the affinity of Escherichia coli mismatch repair (MMR) protein MutS for DNA damaged by an intercalating compound. We examined the binding properties of this protein with various DNA substrates containing a single centrally located adduct of ruthenium(II) arene complexes [(eta(6)-arene)Ru(II)(en)Cl][PF(6)] [arene is tetrahydroanthracene (THA) or p-cymene (CYM); en is ethylenediamine]. These two complexes were chosen as representatives of two different classes of monofunctional ruthenium(II) arene compounds which differ in DNA-binding modes: one that involves combined coordination to G N7 along with noncovalent, hydrophobic interactions, such as partial arene intercalation (tricyclic-ring Ru-THA), and the other that binds to DNA only via coordination to G N7 and does not interact with double-helical DNA by intercalation (monoring Ru-CYM). Using electrophoretic mobility shift assays, we examined the binding properties of MutS protein with various DNA duplexes (homoduplexes or mismatched duplexes) containing a single centrally located adduct of ruthenium(II) arene compounds. We have shown that presence of the ruthenium(II) arene adducts decreases the affinity of MutS for ruthenated DNA duplexes that either have a regular sequence or contain a mismatch and that intercalation of the arene contributes considerably to this inhibitory effect. Since MutS initiates MMR by recognizing DNA lesions, the results of the present work support the view that DNA damage due to intercalation is removed from DNA by a mechanism(s) other than MMR.     

The structure and DNA-binding properties of Mgm101 from a yeast with a linear mitochondrial genome

To study the mechanisms involved in the maintenance of a linear mitochondrial genome we investigated the biochemical properties of the recombination protein Mgm101 from Candida parapsilosis. We show that CpMgm101 complements defects associated with the Saccharomyces cerevisiae mgm101–1^ts mutation and that it is present in both the nucleus and mitochondrial nucleoids of C. parapsilosis. Unlike its S. cerevisiae counterpart, CpMgm101 is associated with the entire nucleoid population and is able to bind to a broad range of DNA substrates in a non-sequence specific manner. CpMgm101 is also able to catalyze strand annealing and D-loop formation. CpMgm101 forms a roughly C-shaped trimer in solution according to SAXS. Electron microscopy of a complex of CpMgm101 with a model mitochondrial telomere revealed homogeneous, ring-shaped structures at the telomeric single-stranded overhangs. The DNA-binding properties of CpMgm101, together with its DNA recombination properties, suggest that it can play a number of possible roles in the replication of the mitochondrial genome and the maintenance of its telomeres.     

Nucleotide excision repair efficiency in quiescent human fibroblasts is modulated by circadian clock

The efficiency of Nucleotide Excision Repair (NER)process is crucial for maintaining genomic integrity because in many organisms, including humans, it represents the only system able to repair a wide range of DNA damage. The aim of the work was to investigate whether the efficiency of the repair of photoproducts induced by UV-light is affected by the circadian phase at which irradiation occurred. NER activity has been analyzed in human quiescent fibroblasts (in the absence of the cell cycle effect), in which circadian rhythmicity has been synchronized with a pulse of dexamethasone. Our results demonstrate that both DNA damage induction and repair efficiency are strictly dependent on the phase of the circadian rhythm at which the cells are UV-exposed. Furthermore, the differences observed between fibroblasts irradiated at different circadian times (CTs) are abolished when the clock is obliterated. In addition, we observe that chromatin structure is regulated by circadian rhythmicity. Maximal chromatin relaxation occurred at the same CT when photoproduct formation and removal were highest. Our data suggest that the circadian clock regulates both the DNA sensitivity to UV damage and the efficiency of NER by controlling chromatin condensation mainly through histone acetylation.     

Equivalence of citizen science and scientific data for modelling species distribution of birds from a tropical savanna

The Wallacean deficit continues to be a challenge to species distribution modelling. Although some authors have suggested that data collected by citizen scientists can be relevant for a better understanding of biodiversity, to our knowledge, no work has quantitatively tested the equivalence between scientific and citizen science data. Here, we investigate the hypothesis that data collected by citizen scientists can be equivalent to data collected by professional scientists when generating species spatial distribution models. For 42 bird species in the Cerrado region we generated and compared species distribution models based on three data sources: (1) scientific data, (2) citizen science data and (3) sample size corrected citizen science data. To test our hypothesis, we compared the equivalence of these datasets. We rejected the hypothesis of equivalence for about one-third (38%) of the evaluated species, revealing that, for most of the species considered, the models generated were equivalent irrespective of the data set used. The distances between centroids of the models that were equivalent were on average smaller than the distances between non-equivalent models. Also, the direction of change in the models showed no pattern, with no trend towards more populated regions. Our results show that the use of data collected by citizen scientists can be an ally in filling the Wallacean deficit gap. In fact, the lack of use of this wide range of data collected by citizen scientists seems to be an unjustified caution. We indicate the potential of using citizen science data for modelling the distribution of species, mainly due to the large set of data collected, which is impracticable for scientists alone to collect. Conservation measures will be favoured by the union of professional and amateur data, aiming for a better understanding of species distribution and, consequently, biodiversity conservation.     

An HRP study in the cat of pathways which may interconnect the two ventrobasal complexes

Possible direct or indirect connections between the two VB thalamic complexes were investigated using the HRP technique. Labelled cells were found ipsilaterally in the NCP and in NRT following injections n the VB complex and in the ipsilateral NRT and in contralateral NCP following injections in NCP. No labelling of contralateral VB complex was ever found. A pathway involving NRT and NCP is suggested to support the possibility of indirect connections between the two thalami and the functional implications of the described projections are discussed.