DNA repair is an active cellular process to respond to constant DNA damage caused by metabolic processes and environmental factors. Since the outcome of DNA damage is generally adverse and long term effects may contribute to oncogenesis, cells have developed a variety of DNA repair mechanisms, which operate depending on the type of DNA damage inflicted. At least 15 Fanconi anemia (FA) proteins interact in a common pathway involved in homologous recombination. Inherited homozygous mutations in any of these FA genes cause a rare disease, Fanconi anemia, characterized by congenit al abnormalities, progressive bone-marrow failure and cancer susceptibility. Heterozygous germline FA mutations predispose to various types of cancer. In addition, somatic FA mutations ha ve been identified in diverse cancer types. Evidence exists that cells deficient in the FA pathway become dependent on alternative pathways for survival. Additional inhibition of such alternative pathways is thus expected to result in cell death, creating a relationship of synthetic lethality. Identifying these relationships can reveal yet unknown mechanisms of DNA repair and new targets for therapy., T. Hucl, E. Gallmeier., and Obsahuje bibliografii a bibliografické odkazy
3H thymidine was injected into pregnant mice in order to label the DNA in the dividing Purkinje cell (PC) precursors of the embryonic cerebellum. The retention of 3H-DNA was evaluated in PC nuclei of animals at the age of 25 days, 3, 6 or 9 months by light microscope autoradiography. The number of silver grains decreased in the whole nuclei by 13.6 % and 19.6 % in animals 6- and 9-month-old, respectively. In the nucleolar region, the loss of DNA radioactivity was more profound; the silver grain counts decreased by 22.6 % and 29.1 % in 6-and 9- month-old animals, respectively. No significant differences in the volume and dry mass concentration were found in the PC nuclei of 25 PD and 9 PM old animals. Therefore, the observed changes in grain density counts represent the actual measure of 3H-DNA loss, and /or "spontaneous" renewal of the DNA molecule in PC nuclei, as well as its higher expression in the nucleolar region. Furthermore, it follows from the comparison of our data with those present in the literature, that DNA synthesized in nerve cell precursors before their withdrawal from the mitotic cycle is more stable than that synthesized in postmitotic neurones. This suggests that the repair of DNA in mature neurones might be of an error-prone type.