Zickler Lecture 2004
Pharmacological Sciences Home
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About the Lecture
The instructions for life are laid down in the genetic information contained within the DNA molecule that harbors all our genes and is located in the nucleus of every cell of our body. Importantly, these instructions should function properly during the entire life span of an organism and should be transmitted faithfully over subsequent generations. However, ubiquitous DNA-damaging agents such as UV light and X-rays and numerous natural and man-made chemicals continuously threaten DNA integrity. In addition, DNA suffers constantly from the damaging effects of reactive oxygen species generated by our own respiration. Moreover, DNA has an intrinsic chemical instability, leading to spontaneous loss of coding information. Spectacular progress in recent years has revealed the dramatic impact of DNA damage on human health and identified damage to DNA as a major cause of onset of cancer, ageing and inherited defects. Ingeniously, to prevent the deleterious consequences of DNA injury the DNA carries also instructions for its own care-taking apparatus. An important component of this self-protecting mechanism is comprised of an intricate network of DNA damage repair systems. These systems attempt to repair the DNA lesions before they give rise to permanent changes in the genetic code leading to cancer and inborn defects or cause cell death or permanent growth arrest contributing to ageing. One of the most versatile repair pathways is called nucleotide excision repair. Patients carrying inborn defects in this repair process suffer from extreme sensitivity to UV radiation in sunlight and to many chemical agents, frequently develop cancer and some patients exhibit dramatic signs of premature aging. The lecture will highlight our current understanding of DNA damage, repair and the overall condition of our genes from studies involving transgenic mice and the impact of DNA damage and repair on health, cancer and aging-related diseases. About the Speaker H. J. Hoeijmakers (born 1951) studied biology at Nijmegen University , the Netherlands . His Ph.D. work (until 1979) on trypanosomes at the University of Amsterdam , resolved the molecular basis for antigenic variation of sleeping sickness. In 1980, he joined the Institute of Genetics of the Erasmus University to work on DNA repair. His team cloned the first of many subsequent human DNA-repair genes, discovered the strong evolutionary conservation of DNA repair systems, elucidated the basis of several human nucleotide-excision repair (and basal transcription) syndromes, generated many DNA-repair mouse mutants and discovered a link between repair and ageing. Recently, his group generated the first mouse mutant with intrinsic defects in the biological clock. His work has been awarded several times including the Louis Jeantet Prize (1995), The Spinoza award (1999), and the Descartes-Huijgens award (2000), the Josephine Nefkens' award (2001). In 1993, he became the Professor of Molecular Genetics, and since 1999 he has been the head of the Institute of Genetics at the Erasmus University. |
