Objective
MOLECULAR AND GENETIC ANALYSIS OF DNA DAMAGE IN MAMMALIAN CELLS.
IT IS NOW WIDELY RECOGNIZED THAT REPAIR AND MISREPAIR OF DNA LESIONS REPRESENT VERY IMPORTANT FACTORS IN THE EXPRESSION OF GENETIC DAMAGE. THE RECENT ADVANCES IN MOLECULAR AND CELLULAR GENETICS, SUCH AS GENE CLONING AND PRODUCTION OF MONOCLONAL ANTIBODIES, HAVE OPENED NEW AVENUES TO APPROACH THE PROBLEMS OF STUDYING THE RADIATION-INDUCED DNA LESIONS IN HUMAN CELLS AND THEIR BIOCHEMICAL AND BIOLOGICAL EFFECTS. THE UTILIZATION OF SPECIFIC ANTIBODIES PERMITS NOW THE IDENTIFICATION OF SINGLE ALTERATIONS IN THE STRUCTURE OF THE DNA.THE SCARCITY OF DNA REPAIR MUTANTS IN MAMMALIAN CELLS CAN BE PARTIALLY OVERCOME BY ANALYSING EITHER DIRECTLY OR BY MEANS OF MONOCLONAL ANTIBODIES THE MULTIENZYMATIC SUBCELLULAR SYSTEMS RESPONSIBLE FOR THE FUNDAMENTAL STEPS OF THE DNA REPAIR PROCESS.
FURTHERMORE THE AVAILABILITY OF SPECIFIC INHIBITORS TO KEY ENZYMATIC REACTIONS (SUCH AS APHIDICOLIN FOR DNA POLYMERASE) PERMITS THE ANALYSIS OF THE ROLE OF THE TARGET MOLECULES OF THE REPAIR PROCESS, THE SELECTION OF MUTANT CELL LINES RESISTANT TO HIGH LEVELS OF THE INHIBITOR AND THE ACQUISITION OF A QUALITATIVE AND QUANTITATIVE MODIFICATION OF GENE PRODUCTS.
Poly(ADP-ribose)polymerase (pADPRP) function, in DNA replication and repair, was investigated by analysing the activity, structure and expression of the enzyme in different cellular systems. The activity and structure of DNA ligase from mammalian cells and from patients with Bloom's syndrome and Faconi's anaemia was also analysed. Cellular and genetic characterisation of Ultra violet induced Chinese Hamster Ovary (CHO) mutants was investigated with the mapping of human genes involved in DNA repair. The analysis of genetic instability in patients with clinical features suggests alterations in DNA repair.
A study of proteins (and their structures) involved in deoxyribonuleic acid (DNA) replication and repair in animal cells has been carried out. The isolation of mammalian mutant cells altered in DNA metabolism, determination of their sensitivity to mutagens and the molecular analysis of modified DNA have been achieved.
THE STUDY WILL BE PURSUED ALONG THE FOLLOWING RESEARCH LINES:
1-PROTEINS AND STRUCTURES INVOLVED IN DNA REPLICATION AND REPAIR IN ANIMAL CELLS.
2-ISOLATION AND MAMMALIAN MUTANT CELLS ALTERED IN DNA METABOLISM AND SENSITIVITY TO MUTAGENS.
3-MOLECULAR ANALYSIS OF DAMAGED DNA.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences genetics DNA
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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Coordinator
00185 Roma
Italy
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