题 目: Molecular measures of human aging and a new cohesin model
报告人：Dr. Mitsuhiro Yanagida（OIST; NAS, USA）
时 间： 2018.5.17（周四），下午16:00
Dr. Yanagida received his doctorate in science from the University of Tokyo in 1970. He was Professor of Biophysics at Kyoto University from 1977 to 2004, where he served as Dean of Graduate School of Biostudies from 2001 to 2003. After retiring from Kyoto University and becoming Professor Emeritus, he has been Professor of the G0 Cell Unit at the Okinawa Institute of Science and Technology. Yanagida is an Honorary Fellow of the Society of Biology since 2010 and foreign associate of the National Academy of Sciences, USA since 2012. He received many awards including the Order of Culture (2011) and the Imperial Prize of the Japan Academy (2003).
Dr. Yanagida is a molecular biologist noted for his work to decipher how chromosomes in a cell are correctly segregated during the cell cycle, to split perfectly into two daughter cells. He has discovered a host of genes in yeast that are critical to this fundamental process of life and revealed the structure of centromeres in the yeast Schizosaccharomyces pombe, and the vital proteins that bind to it to achieve separation. He has studied the mechanisms of chromosome segregation for a number of years, recently starting work on cell maintenance in the quiescent stage G0.
Human aging is a highly complex biological process, exhibiting great individual variation. While distinguishing young and elderly people visually is easy, it was not possible to distinguish blood, saliva and urine samples from young or elderly donors. Using LC-MS, we identified metabolites in blood (43), saliva (17) and urine (50) that show significant differences in abundance between young (<40 yr) and elderly (>80 yr). Moreover, we discovered 7 unknown, but highly-related blood metabolites linked to aging. Age-linked metabolite information will be very useful in monitoring human aging when combined with the Principal Component Analysis, which provides the synthetic degree of aging. I shall present correlation of metabolites with different aspects of human aging.
The heterodimeric cohesin SMC complex embraces duplex DNA and is associated with Rad21, which is cleaved in mitotic anaphase by protease separase/Cut1, followed with the release and segregation of chromosomal DNAs. We identified extragenic suppressors for separase ts mutants using whole genome sequencing. Our unexpected finding is that cleavage of Rad21 is largely dispensable if suppressor causes physical disorders of cohesin interfaces among essential subunits. The predicted disorders provide insights into a DNA ‘hold and release’ model in which hinge and head of SMC subunits are proximal to form arched coiled coils that close or open by their orientation. The model sharply distinct from the prevailing ring model explains features of cohesin.