Zickler Lecture 1995
Zickler Lecture - 1995
DEPARTMENT OF PHARMACOLOGICAL SCIENCES
About the Zickler Lecture Series / Past Zickler Lecturers
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THE SEVENTH ANNUAL ZICKLER LECTURE
DIRK BOOTSMA, Ph.D.
Professor of Genetics
DNA REPAIR:
Thursday, December 7, 1995 |
About the Speaker
Dirk Bootsma is Professor of Genetics in the Faculty of Medicine of the Erasmus University at Rotterdam , The Netherlands. He studied biology at the University of Utrecht (1953-1960) and received his Ph.D. degree from the University of Leiden for a study of the influence of X-irradiation on the division cycle of cultured human cells. This work was performed at the Medical Biological Laboratory at Rijswijk . Here he started his work in the field of somatic cell genetics with emphasis on the genetic basis of DNA repair. This resulted in the discovery of the complementation group in xeroderma pigmentosum and later in the unraveling of the genetic defects in several DNA repair deficiency syndromes. Professor Bootsma is a member of the Netherlands Academy of Arts & Sciences, the Council of the European Molecular Biology Organization (EMBO), and the Academiae Europaeae. He was awarded the Shell Prize in the Life Sciences in 1986, the Prix Lacassagne of the Lique Nationale contre le Cancer de France in 1991, and the Prix Louis Jeantet de Medicine in 1995.
Bootsma and his group study the genetic and molecular basis of DNA repair processes and inborn repair syndromes. This work was initiated after Cleaver's discovery in 1968 of a DNA repair defect in the cancer prone disorder xeroderma pigmentosum (XP). This work resulted in the identification of eight distinct complementation groups in this disorder and provided the basis for genetic studies of DNA repair in mammals. Jan Hoeijmakers, a member of Professor Bootsma's group, cloned the first human DNA excision repair gene (ERCCI), a protein that proved to be homologous to the yeast excision repair protein RAD10, providing the first indication for the strong evolutionary conservation of the system.
Other human repair genes that shed light on XP and other DNA repair syndromes, including Cockaye's syndrome and trichothiodystrophy, were subsequently cloned. A clue for the molecular explanation of these seemingly unrelated manifestations came from the discovery that the ERCC3 repair helicase is simultaneously involved in transcription. Recently, the generation of mouse models for various repair disorders, using gene targeting in embryonal stem cells, resulted in the generation of mice carrying defects in ERCC1, ERCC3, ERCC6, and other repair genes.