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Lynch syndrome is an inherited disease leading to the development predominantly of colorectal cancer (CRC). The crucial cause is malfunction of DNA mismatch repair that is characterized by high level of microsatellite instability; however, new knowledge of two MSI modes (types A and B) suggests a more complex molecular basis of this syndrome. To investigate, whether the extensive alterations in individual MSI markers (type B) can indicate the potential deficiency of DNA double-strand break (DSB) repair in Lynch-syndrome-related tumours, we evaluated the MSI type and alterations in the MRE11 and RAD50 repeats that are associated with the reduced protein expression and functional impairment of the MRE11-RAD50-NBS1 (MRN) complex. Of 27 CRCs, 21 samples manifested type B in at least one MSI+ marker. From type B tumours, the genetic alterations were identified in 16 (76%) samples; seven, one and eight cases manifested mutations in MRE11, RAD50 and both genes, respectively. However, predominantly biallelic MRE11 alterations with simultaneously developed RAD50 mutations impaired the protein expressions with different intensity and location in tumour. Of six tumours presenting changes

Background and Aims The objective of this study was to analyse the role of nitric oxide (NO) in relation to reactive oxygen species (ROS) production and root growth inhibition in the early response of barley root tip to cadmium. Methods We used cell-permeable NO-binding dye DAF-2DA for the NO localization and cellimpermeable dye DAR-4M for the quantification of NO in barley root apex. Results A considerable increase in NO production was detected in the transition zone of root tips already 30 min after the immersion of barley roots into 15 μM Cd. This Cd-induced NO generation further increased during the recovery period and reached its maximum level 2 h after the short-term treatment. At this stage an enhanced Cd-induced NO generation was observed in the meristematic, transition and in the beginning of elongation zone in comparison with control roots. Inhibitor of NO synthase activity markedly reduced root growth in control seedlings and had a synergistic growth inhibitory effect with Cd. On the contrary, this Cdinduced root growth inhibition was markedly alleviated by the NO donor. Exposure of roots to Cd markedly increased the production of ROS in the proximal elongation zone of root. While NO did not affect ROS generation, inhibition of its synthesis slightly decreased ROS generation in both control and Cd-treated roots. Conclusions Our results revealed that enhanced NO production is a very early response of barley root to Cd stress and it is involved in the regulation of root growth mitigating Cd-induced root growth inhibition.