STRUCTURAL STUDIES OF S CEREVISIAE MONOPOLIN COMPLEX COMPONENTS

Cornell University, Ithaca NY

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Meiosis is a specialized two-step process of chromosome division that results in the production of haploid gametes from a diploid progenitor cell. During the first step (meiosis I), homologous pairs of sister chromatids must align and segregate to opposite poles. Later, in meiosis II, the two chromatids of each pair segregate to opposite poles. In S. cerevisiae, the monopolin complex is partially responsible for ensuring that sister chromatids behave differently in meiosis I and II, orienting towards the same pole during meiosis I. It is thought that the monopolin complex either fuses the kinetochores of sister chromatids, or prevents one sister from attaching to microtubules in the spindle. We are studying the physical mechanism for monopolin complex function using structural and biochemical methods. We hope to elucidate the exact subunit composition of this complex, as well as the timing of assembly and how the complex binds to the kinetochore. In addition, we hope that structural studies of this complex will lead to physical picture of how the complex achieves its function: whether it fuses sister kinetochores, prevents attachment of one sister chromatid, or acts through a combination of these mechanisms. Finally, we hope to study the related function of a monopolin subcomplex consisting of two of the four subunits. This subcomplex, also called cohibin, is important for preventing recombination in the highly repetitive rDNA, and possibly acts through a DNA cross-linking mechanism.