This application seeks continuing support for the on-going Chromosome Metabolism and Cancer Training Program that trains researchers exploring the links between chromosome metabolism andcancer. Advances in the studies of genes and genomes have greatly facilitated the understanding of chromosome metabolism (gene expression, chromatin assembly, segregation, telomeres and centromeres, DNA repair, etc.) and illustrated its importance in cancer initiation and progression. The 25 training faculty are experts in this area from the Basic Sciences Human Biology Divisions of the Fred Hutchinson Cancer Research Center. Many are leading scientists in their own fields, and together they form a cohesive group that approaches the issue from different but complementing angles. They include structural biologists in addition to molecular and cellular biologists, and utilize various model organisms such as nematode, fly and yeast in addition to vertebrates and cultured cells in their studies. The breadth and depth of this program should help generate excellent young scientists with creative approaches to understanding cancer mechanisms. Two predoctoral positions are requested to maintain the current level of support of this successful program that was initiated ten years ago following the formation of the Molecular and Cell Biology (MCB) Graduate Program. The postdoctoral positions will also be maintained at the current level of five. Predoctoral trainees will be recruited among the MCB students, who enter the PhD program through vigorous competition and are among the best in the nation. Postdoctoral trainees are drawn from an outstanding pool of fellows working with CMTP Faculty. Predoctoral students are appointed to the training grant after they have chosen a permanent laboratory and completed lab rotations and a portion of their required coursework. Postdoctoral training consists of independent research, supplemented by rigorous quarterly presentations in front of training grant faculty and experience in organizing CMTP-sponsored seminars. In addition, all trainees will benefit from the rich activities available for researchers at this Center, including the strong interdisciplinary programs that expose basic scientists to clinical and public health aspects of cancer. It is hoped that this program will create young scientists with in-depth understanding of chromosome metabolism and commitment to explore its various links to cancer cause, cure and prevention.