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THE COUNCIL FOR TOBACCO RESEARCH-U.S.A., INC. 900 111IRD AVENUE NEW YORK. N. Y. 10022 Memorandum To: Dr. H.McAllister and Staff From: D.H:,Ford Re: Site Visit with Dr.Howard Lieberman, Columbia University.Center for Radiological Research, July 14, 1993 Grant No.3355R1 entitled "Molecular Aspects of DNA Repair in S.pombe" Goal: To obtain a further understanding of the mechanisms involved in DNA repair. This may be expanded to include an understanding of th ose factors which influence transcription. In undertaking these goals Dr. Lieberman is focusing on determining which genes in S.pombe control radioresistance and cell cyc}.le progressical. Since his completed studies have demonstrated that there are 3 radioresistant derivitives which contain unique suppressor loci, his current focus will be on determining how they provide resistance, particularly since they lack the ability to induce a delay at the G2 stage in the cell cydle (a period in which DNA repair may occur). Results: Dr. Liebrman's use of the yeast, S. pombe as a research tool is simply because it is an easier cell type to work with for studies of DNA repair than mammalian cells, besides being less expensive. Progress appears to be excd.llent (1 abstract, one paper in press and one submitted recently to GENETICS on 6/15/93. The latter;is entitled "Extragenic suppressors of S.pombe rad9 mutations uncouple radio- resistance, hydroxyurea sensitivity and cell cycle checkpoint control." Dr. Lieberman has produced a mutant S.pombe cell type with a mutation in the rad9 gene which makes the cells sensitive to ionizing radiation, UV light and hydroxyurea as ompared to wild-type yeast strains. Further, the mutant cells are moderately hypomutable to UV and unable to delay initiation of mitosis or delay cycling.in the G2 phase. Three radioresistant derivitives of (, these mutant cells which contain the mutant rad9::ura 4 gene have been detected and each found to contain a unique single extragenic suppressor which provided the radioresistance to irradiation and UV. He has named these suppressors srrl-l, srr2-1 and srr3-1. Cross mating of strains containing srrl-l with srr2-1 indicated that their loci were different and that they are unlinked. Similar rsults occurred when srr2-1 and srr3-1 were crossed. However, a cross between srrl-2 and 3-1 indicated that they were genetically linked. However, since the 3 suppressors of the rad9::ura4 radiosensitivity were unable to stop the cell cycle progression at the G2 checkpoint (to allow DNA repair mechanisms to operate), the confering of radioresistance has to occur via some other method...a question now being investigated by Dr. Lieberman. Comment: An active and exciting project which appears to be progressing well under the direction of a young enthusuastic investigator. This is a difficult question to solve and one which is being investigated by many researchers. The solution is important not only for a better understanding of cell biology but of the evolution of maligant cells. DHF