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Cell Cycle and Cancer Biology Research Program

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OMRF scientists pinpoint body's system for preventing chromosomal defects

Michael E. Dresser, M.D./Ph.D. Associate Member, Cell Cycle and Cancer Biology Research Program Adjunct Associate Professor, Department of Cell Biology, University of Oklahoma   Health Sciences Center

Research Interests
Chromosome abnormalities that arise during the development of sperm and eggs can cause infertility, birth defects and increased predisposition to cancer. To prevent these abnormalities, chromosomes of each pair must recognize one another, move together, align closely, exchange parts and then segregate away from one another during meiosis to form the reduced genome of sperm and eggs, thus preparing the genome for the next generation. My laboratory uses the yeast Saccharomyces cerevisiae to identify the molecular mechanisms that carry out these activities.

Our major focus at present is to understand the contribution of telomeres to these processes. Telomeres are structures that stabilize the ends of chromosomes and play roles in aging and prevention of cancer. During meiosis, telomeres draw all chromosomes into a single cluster that persists for a short time, just when chromosome pairs are becoming closely aligned. This event occurs in humans, plants, amphibians, yeast and other organisms, but its purpose remains unexplained. Recently, we have discovered that telomeres tug chromosomes rapidly around the nuclear envelope throughout meiosis, and our analyses indicate that by understanding these movements we will gain insights into currently unknown, fundamental cellular mechanisms that preserve the genome.

We first discovered that Ndj1p is a telomere protein which appears only in meiosis. When Ndj1p is defective, telomeres fail to form the cluster, the movements are slowed, chromosomes are slow to align and chromosomes missegregate, leading to aneuploidy of the sort that causes infertility and birth defects. Using an approach that combines genetics, molecular genetics and high-resolution fluorescence and electron microscopy, we have identified new proteins required to make the cluster, including Mps3p and Csm4p which also localize to telomeres in meiosis. Mps3p is a member of a family of proteins implicated in chromosome and nucleus positioning in various organisms, supporting the idea that the molecular mechanisms we are uncovering are fundamental and widespread.

We have developed and patented new methods of microscopy to track movements in live cells and have found that the telomere-promoted movements are more important than telomere clustering in generating proper chromosome pairing and segregation, providing a new perspective on how the genome is preserved for delivery across generations.

Joined OMRF Scientific Staff in 1989.

Mailing Address
Cell Cycle and Cancer Biology Research Program, MS 48
Oklahoma Medical Research Foundation
825 N.E. 13th Street
Oklahoma City, Oklahoma 73104

Contact Information
Phone: (405) 271-7682
Fax: (405) 271-7312
E-mail: Michael-Dresser@omrf.org