Mechanisms of Sister Chromatid Pairing

Lehigh University, Bethlehem PA

Investigators

Abstract

The continuance of life through cell division requires that each daughter cell receive one and only one chromosome set from the parent cell. High fidelity DNA replication and chromosome segregation are fundamental components to this process. During DNA replication, each parental chromosome is exactly duplicated. At the same time, the resulting chromosomes (called sister chromatids) become tightly paired along their length. This pairing between chromatids identifies the sisters over time. Upon cell division, the pairing mechanism is inactivated and the sisters segregate away from each other into the newly forming daughter cells. This is the hallmark of proper cell division. Defects in sister chromatid pairing have dire consequences for the organism, causing severe abnormalities of many kinds. This project will help characterize the mechanism by which sister chromatid pairing is established. CTF7 (also called ECO1) is an essential component of the sister chromatid pairing pathway in yeast and Ctf7p is highly conserved throughout evolution. The goals of this research are to 1) map Ctf7p protein interaction domains required for sister chromatid pairing, 2) test molecular models of how sister chromatids are paired, and 3) identify new components that are required for sister chromatid pairing. These goals will be accomplished using biochemical, molecular, genetic and high-resolution light microscopy approaches in yeast cells. The successful completion of these goals will enable the investigator to build a testable physical model of how sister chromatids become paired and elucidate the regulatory mechanisms involved. In addition to advancing the understanding of chromosome segregation, this research program will strengthen the scientific infrastructure at Lehigh University, an institution with a high percentage of undergraduate students. Students and post-doctoral fellows will acquire new intellectual and technical skills from this project.