Objective
All organisms have evolved an intricate network of DNA repair systems that enables them to recognise and eliminate lesions in the DNA induced by the action of numerous chemical and physical agents.
The primary goal of the research of which this joint project is a part is: to unravel the molecular mechanisms, specificity and fidelity of repair of DNA damage in mammalian cells; and elucidate the molecular defects in human genetic disorders associated with DNA repair deficiencies: xeroderma pigmentosum (XP), Cockayne's syndrome (CS), and trichothiodystrophy (TTD), and Progeria (PR), a premature ageing syndrome in which deficient DNA repair might be involved. These diseases are characterised by sun (UV) sensitivity, frequently neurological abnormalities, poor development, for XP predisposition to skin cancer and, in some diseases, premature ageing. Mouse models for human DNA repair deficiencies will be generated to assess the biological impact of these systems and for genotoxicity testing. The approaches followed include inducing specific DNA repair defects in the mouse germline by gene targeting technologies. Insight into DNA repair mechanisms is relevant for understanding the effect of DNA damage on vital processes such as transcription, replication and recombination. Indirectly these processes affect the origin of inborn defects, carcinogenesis, genome stability and ageing.
DNA repair has been traditionally a strong area in Europe and the current research project will introduce two Russian research groups to the European collaboration on DNA repair.
Topic(s)
Call for proposal
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3000 DR Rotterdam
Netherlands