Histones and Cell Division Control

Michigan State University, East Lansing MI

Investigators

Abstract

Intellectual merit. Faithful segregation of the duplicated genome to daughter cells is key to species perpetuation. If a human cell receives an uneven number of chromosomes after cell division, serious disorders arise, while in many other species, selective gain or loss of certain chromosomes is essential for key developmental functions. A detailed understanding of how eukaryotes ensure segregation fidelity is thus of tremendous significance. Faithful segregation requires that each chromosome is attached to a cellular apparatus that ensures their separation; during the process of separating these so-called sister chromatids, tension is generated. Sensing this tension is important for the dividing cell to ascertain that the chromosomes have been properly attached, and defects in tension sensing may bring about an uneven distribution of chromosomes and cell death. It has been recently demonstrated that the tension sensing function of the model organism Saccharomyces cerevisiae depends critically on histone H3, which recruits another protein named Sgo1p. Mutations of a Tension Sensing Motif in histone H3 impair the ability of cells to respond to defects in tension. The conclusion that an integral component of the chromatin actively participates in the process of separating sister chromatids profoundly changes a long-held view that chromosomes are passively distributed to daughter cells. This project aims to delineate the mechanistic details of how chromatin recruits Sgo1p, and whether and how this recruitment might be regulated at a molecular level. It will be determined how histone H3 recruits Sgo1p ensure a functional tension sensing mechanism and how H3 interacts with cellular protein complexes that modify chromatin. Broader Impact. This work will have impacts that are beyond the scientific merits in that the research project will involve not only graduate students, who will be exposed to the highest standard of scientific research training and ethics, but also undergraduate students, who will have first-hand research experiences that will likely make deep impacts on the choice of their career paths. Furthermore, these young scientist-hopefuls will be mentored by the PI and other more senior graduate students; the latter will thus acquire invaluable mentorship skills before they assume an independent role in research and/or teaching.