http://http://dspace.unitus.it:80 The DSpace digital repository system captures, stores, indexes, preserves, and distributes digital research material. Fri, 24 May 2013 18:01:11 GMT 2013-05-24T18:01:11Z http://hdl.handle.net/2067/1343 Title: The novel human gene aprataxin is directly involved in DNA single-strand-break repair. Authors: Mosesso, Pasquale; Piane, Maria; Palitti, Fabrizio; Pepe, Gaetano; Penna, Sabrina; Chessa, Luciana Abstract: The cells of an ataxia-oculomotor apraxia type 1 (AOA1) patient, homozygous for a new aprataxin mutation (T739C), were treated with camptothecin, an inhibitor of DNA topoisomerase I which induces DNA single-strand breaks. DNA damage was evaluated by cytogenetic analysis of chromosomal aberrations. The results obtained showed marked and dose-related increases in induced chromosomal aberrations in the patient and her heterozygous mother compared to the intrafamilial wild-type control. The alkaline comet assay confirmed this pattern. Moreover, the AOA1 cells did not show hypersensitivity to ionizing radiation, i.e. X-rays. These findings clearly indicate the direct involvement of aprataxin in the DNA single-strand-break repair machinery. Description: L'articolo è disponibile sul sito dell'editore: http://www.springerlink.com/ Fri, 31 Dec 2004 23:00:00 GMT http://hdl.handle.net/2067/1343 2004-12-31T23:00:00Z http://hdl.handle.net/2067/1349 Title: Potassium Bromate but not X-ray cause unexpectedly elevated levels of DNA breakage similar to those induced by ultraviolet light in Cockayne syndrome (CS-B) fibroblast Authors: Mosesso, Pasquale; Penna, Sabrina; Pepe, Gaetano; Lorenti Garcia, Claudia; Palitti, Fabrizio Abstract: It has been previously reported that the elevated accumulation of repair incision intermediates in cells from patients with combined characteristics of xeroderma pigmentosum complementation group D (XP-D) and Cockayne syndrome (CS) XP-D/CS fibroblasts following UV irradiation is caused by an "uncontrolled" incision of undamaged genomic DNA induced by UV-DNA-lesions which apparently are not removed. This could be an explanation for the extreme sensitivity of these cells to UV light. In the present study, we confirm the immediate DNA breakage following UV irradiation also for CS group B (CS-B) fibroblasts by DNA migration in the "comet assay" and extend these findings to other lesions such as 8-oxodeoxyguanosine (8-oxodG), selectively induced by KBrO3 treatment. In contrast, X-ray exposure does not induce differential DNA breakage. This indicates that additional lesions other than the UV-induced photoproducts (cyclobutane pyrimidine dimers, CPD, and 6-pyrimidine-4-pyrimidone products, 6-4 PP), such as 8-oxodG, specifically induced by KBrO3, are likely to trigger "uncontrolled" DNA breakage in the undamaged genomic DNA in the CS-B fibroblasts, thus accounting for some of the clinical features of these patients Description: L'articolo é disponibile sul sito dell'editore: http://www.karger.com Wed, 31 Dec 2003 23:00:00 GMT http://hdl.handle.net/2067/1349 2003-12-31T23:00:00Z http://hdl.handle.net/2067/1341 Title: Methyltrioxorhenium catalysed synthesis of highly oxidised aryltetralin lignans with anti-topoisomerase II and apoptogenic activities Authors: Fiani, Cinzia; Belfiore, Maria Cristina; Gualandi, Giampiero; Penna, Sabrina; Mosesso, Pasquale Abstract: A novel and efficient procedure to prepare highly oxidised aryltetralin lignans, such as isopodophyllotoxone and (-)-aristologone derivatives, by oxidation of podophyllotoxin and galbulin with methylrhenium trioxide (MTO) and novel MTO heterogeneous catalysts is reported. It is noteworthy that in the case of isopodophyllotoxone derivatives the functionalisation of the C-4 position of the C-ring and the ring-opening of the D-lactone moiety increased the activity against topoisomerase II while causing the undesired inhibition of tubulin polymerisation to disappear. The novel (-)-aristologone derivatives showed apoptogenic activity against resistant human lymphoma cell lines. Description: L'articolo è disponibile sul sito dell'editore: http://www.sciencedirect.com Fri, 31 Dec 2004 23:00:00 GMT http://hdl.handle.net/2067/1341 2004-12-31T23:00:00Z