How does a cell repair damaged DNA?

DNA in living cells is constantly subjected to different chemical and physical factors of the environment and to cell metabolites. Some changes altering DNA structure occur spontaneously. This raises the potential danger of harmful mutations that could be transmitted to offspring. To avoid the danger of mutations and changing genetic information, a cell is capable to switch on multiple mechanisms of DNA repair that remove damage and restore native structure. In many cases, removal of the same damage may involve several alternative pathways; this is very important for DNA repair under the most unfavorable conditions. This review summarizes data about all known mechanisms of eukaryotic DNA repair including excision repair (base excision repair and nucleotide excision repair), mismatch repair, repair of double-strand breaks, and cross-link repair. Special attention is given to the regulation of excision repair by different proteins—proliferating cell nuclear antigen (PCNA), p53, and proteasome. The review also highlights problem of bypassing irremovable lesions in DNA.Translated from Biokhimiya, Vol. 70, No. 3, 2005, pp. 341–359.Original Russian Text Copyright © 2005 by Sharova.     

Study of the genesis of pathological EEG patterns in tumor and traumatic lesions of the human brain

Computer-assisted superimposition of the equivalent dipole sources (EDSs) of the main pathological EEG patterns with the results of computer tomography and magnetic resonance imaging of the brain was performed for patients with organic CNS lesions. The greatest degree of structural determination was revealed for local and lateralized (in a traumatic injury) slow waves, whose EDSs mapped to the perifocal zone of the injury focus. The EDSs of epileptiform patterns could be located in the zone of damaged brain substance or in the intact hemisphere (when the limbic structures were damaged), reflecting the formation of secondary functional foci in the latter case. Bilateral paroxysmal patterns were more frequently determined by the functional state of the medial brain structures. The EDSs of pathological (diencephalic, hippocampal) activity were closely associated with the corresponding anatomical brain structures, although without a strict dependence on the degree of their morphological intactness.Translated from Fiziologiya Cheloveka, Vol. 31, No. 1, 2005, pp. 24–32.Original Russian Text Copyright © 2005 by Boldyreva, Sharova, Koptelov, Shchepetkov, Nikitin, Kornienko, Fadeeva.     

Morpho-functional status of the lymph nodes of rats during rehabilitation after exposure to vapors of dimethyl sulfate]

By means of histological methods inferior tracheobronchial lymph nodes have been investigated in 48 Wistar rats in 2 weeks and 3 months after cessation of inhalation of DNSV at maximum possible dose (0.1 mg/m3) for 2 and 14 days. Cell composition of the lymph nodes and cross sections of structural components have been compared. The cross section of the cortex decreases, while that of the medulla increases in comparison with corresponding parameters of the acute experiment. In 2 weeks and 3 months after DMSV effect for 2 days the part (%) of poorly differentiated cells and middle lymphocytes increases, while content of plasma cells in the medullary cords decreases. During rehabilitation after DMSV effect for 14 days a low level plateau is noted (as in the acute experiment). However, in lymphoid nodules++ within content of the poorly differentiated cells and middle lymphocytes in the cortical germinative centers in 2 weeks and 3 months the number of the poorly differentiated and reticular cells increases essentially, as well as mitotically dividing cells (in comparison to the acute experiment). In the medullary cords of the lymph nodes after 3 months of rehabilitation content of immature plasma cells is essentially higher than in 2 weeks of rehabilitation and than in the acute experiment. During rehabilitation the level of cells destruction in the lymph nodes noticeably decreases in comparison to the acute experiment.     

Mechanisms of hypothalamic-pituitary and immune system regulation: The role of gonadotropin-releasing hormone and immune mediators

Different aspects of the reciprocal regulatory influence of systems producing the immune and gonadotropin-releasing hormone (GnRH) in pre- and postnatal ontogeny are discussed in this review. GnRH is a neurohormone synthesized by a small population of neurons located in the anterior hypothalamus, which regulates the secretion of gonadotropines in the anterior lobe of the pituitary gland and they finally regulate the synthesis of sex steroids. Particular attention is given to analysis of the data involving the role of thymic peptides and cytokines in GnRH-system regulation in the normal condition and in the case of inflammation development caused by endotoxines in adult animals. The main prospects of the studies involving the influence of proinflammatory cytokines on GnRH-neuron migration and differentiation in prenatal ontogenesis are also discussed.     

FMRI-EEG estimation of cerebral reactivity to motor tasks in patients with brain tumors

fMRI (1.5 or 3 T) and EEG studies with estimation of reactive responses on motor task (by right or left hand) were performed in 9 patients with tumors localized in frontal lobe of the brain. Results of this investigation were compared with results of the similar study in 12 healthy persons. It was shown that in cases of the brain pathology disorders of functional specialization and increase of diffuse component of reactivity was observed, fMRI-responses had been characterized the more intact reactions than reactive changes of EEG parameters. This specificity was described in cases of afferent loads in damaged hemisphere. Peculiarity of including different spectral bands in forming of EEG responses on motor tasks and changes of fMRI-answer depend on degree of cerebral decompensation, reflected in the of baseline EEG reorganization and degree of motor defect. Predominantly an increase of EEG coherence in delta-band with the predominance of reaction in the damaged hemisphere in cases of addressing any afferent load was observed in patients with severe cerebral decompensation and reflect dominant character of pathological focus forming. This data indicate on the more including of the deep brain structures in process of reactivity in patients compared with healthy persons and confirmed by fMRI-data.