Rad3ATR Decorates Critical Chromosomal Domains with γH2A to Protect Genome Integrity during S-Phase in Fission Yeast

Schizosaccharomyces pombe Rad3 checkpoint kinase and its human ortholog ATR are essential for maintaining genome integrity in cells treated with genotoxins that damage DNA or arrest replication forks. Rad3 and ATR also function during unperturbed growth, although the events triggering their activation and their critical functions are largely unknown. Here, we use ChIP-on-chip analysis to map genomic loci decorated by phosphorylated histone H2A (γH2A), a Rad3 substrate that establishes a chromatin-based recruitment platform for Crb2 and Brc1 DNA repair/checkpoint proteins. Unexpectedly, γH2A marks a diverse array of genomic features during S-phase, including natural replication fork barriers and a fork breakage site, retrotransposons, heterochromatin in the centromeres and telomeres, and ribosomal RNA (rDNA) repeats. γH2A formation at the centromeres and telomeres is associated with heterochromatin establishment by Clr4 histone methyltransferase. We show that γH2A domains recruit Brc1, a factor involved in repair of damaged replication forks. Brc1 C-terminal BRCT domain binding to γH2A is crucial in the absence of Rqh1Sgs1, a RecQ DNA helicase required for rDNA maintenance whose human homologs are mutated in patients with Werner, Bloom, and Rothmund–Thomson syndromes that are characterized by cancer-predisposition or accelerated aging. We conclude that Rad3 phosphorylates histone H2A to mobilize Brc1 to critical genomic domains during S-phase, and this pathway functions in parallel with Rqh1 DNA helicase in maintaining genome integrity

Progressive lens design by discrete shape modelling techniques

The free-form technologies, recently introduced in the manufacturing process of ophthalmic lenses, allow the production of high performance and custom progressive addition lenses (PALs). In this work a method for the parametric design and analysis of PAL, based on discrete shape modelling, is proposed. Both the optical (e.g. power and addition) and the geometrical (e.g. inset, corridor length, amplitude of the distance and near vision area) parameters have been taken into account. In addition the method developed for the analysis of surface optical properties, especially with regard to the astigmatic surface power, has proved an essential tool for the analysis of results. Moreover the exchange data formats for the CNC manufacturing process were described. The influence of different parameters on the optical properties are analyzed and discussed. In this context a key role on the resultant optical properties of the designed PAL is covered by the distribution of the curves in the intermediate area and by the curvature equation along the corridor. Surface power and astigmatic surface power show similar behaviour to other commercial progressive additional lens but, moreover, the designer can specify the distribution of astigmatism in the intermediate region. Compared to the methods proposed in literature, this one shows more opportunities in the design parameters definition and allows highly customized lens, designed on the main habits of the wearer. Finally the method was applied to the manufacturing process of glass mould for PAL and the results of optical parameters measurements are proposed

Prospection and identification of nematotoxic compounds from Canavalia ensiformis seeds effective in the control of the root knot nematode Meloidogyne incognita.

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