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THE MOLECULAR BASIS FOR THE INTERACTION OF RADIATION AND CARCINOGENS WITH THE EUKARIOTIC GENOME AND THE MECHANISM OF REPAIR. STUDIES ON HUMAN AND OTHER EUKARIOTIC CELL CULTURES

Objectif


The effects of ionising radiation and carcinogens in specific regions of the eukaryotic genome, with special reference to the humane genome, have been investigated, and the molecular mechanisms by which deoxyribonucleic acid (DNA) damages are repaired have been clarified.

The aim has been to investigate the effect of ionising radiation and carcinogens in specific regions of the eukaryotic genome with special reference to the humane genome, and to clarify the molecular mechanisms by which deoxyribonucleic acid (DNA) damage is repaired. Investigations have been concentrated on the study of mechanisms leading to DNA damage when chromatin is exposed to ionising radiation and the effect of scavengers on the processes. Furthermore, enzymes involved in repair and recombinational processes have been studied with special attention to the function of the sequence specific enzymes, type I and type II topoisomerase.

Studies on the physiological relevance of master sites have been carried out and the molecular interactions between enzymes and deoxyribonucleic acid (DNA) have been monitored by novel techniques. These techniques have enabled us to prove the existence of a cleaved intermediate in the catalytic cycle, and we have also developed a molecular system which allow us to determine the minimal DNA requirement for both topoisomerase I and II. The importance of topoisomerase DNA interactions, besides their effect in cancer chemotherapy, has been shown by their ability to stabilise the enzyme DNA cleavage intermediates. Cell lines that are resistant to antineoplastic agents, due to modified enzymes, have recently been isolated.

The effects of ionising radiation and carcinogens in specific regions of the eucaryotic genome have been studied with special reference to the human genome, and to clarifying the molecular mechanisms by which deoxyribonucleic acid (DNA) damage is repaired.

Work has been carried out to investigate the effects of ionising radiation and carcinogens in specific regions of the eukaryotic genome, with special reference to the humane genome, and to clarify the molecular mechanisms by which deoxyribonucleic acid (DNA) damage is repaired.
SINGLE EUKARYOTIC GENES ISOLATED AS BIOLOGICALLY ACTIVE CHROMATIN WILL BE USED TO STUDY
A) INTERACTION OF RADIATION AND CARCINOGENS WITH SPECIFIC CHROMATIN STRUCTURES OF THE HUMAN GENOME
B) RECOMBINATION AND REPAIR PROCESSES IN RESPONSE TO IONIZING RADIATION.

EXPECTED BENEFITS

EVALUATION OF GENETIC RISKS FROM IONIZING RADIATION. DETERMINATION OF CELLULAR RADIOSENSITIVIRY AND RELATION TO REPAIR.

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UNIVERSITY OF AARHUS
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RINNGADE 1-3
8000 ARHUS
Danemark

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