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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

How do babies get the right numbers of healthy chromosomes from Mom and from Dad?

Chromosomes are long sections of DNA that reside in the nucleus of every cell in the body. Human cells have 46 chromosomes and, when a cell divides to make two new cells, each chromosome duplicates with one copy going to each new cell in order to maintain this normal chromosome number.

One exception to the rule of equal division happens on the way to making sperm and egg cells. In order for babies to have the right number of chromosomes, each of these cells must have only 23 chromosomes, so that the proper number of 46 is restored when the sperm and egg combine to make an embryo. Unfortunately, this process frequently misbehaves and generates damaged or wrong numbers of chromosomes, problems that can lead to Down syndrome, birth defects and genetic diseases.

In my lab, we want to understand how the chromosome number is reduced from 46 to 23, in order to understand what can, and does, go wrong. The way this reduction occurs is remarkably similar in most organisms, including humans, birds, bees, flowers, and even yeast. So, we use yeast as a "model" organism for our experiments because this is the fastest way to discover the critical parts of the reduction process.

It has long been known that the reduction process starts when each of the 23 chromosomes that originally came from Mom finds and joins with its partner among the chromosomes from Dad. Recently, we have discovered an important new part of how this works. Surprisingly (to us), the ends of each chromosome connects to motors that tug the chromosomes quickly around the inside of the nucleus, helping the correct partners to bump into and recognize each other, but also helping to pull apart chromosomes that should not be partners—sort of like meddlesome chaperones at a middle school dance.

Our next goal is to identify the motors and what controls the movements to further study their roles in preventing chromosomal defects and to identify genetic or environmental factors that might interfere with them. The more we know about how those defects occur, the more likely it is that we can pinpoint ways to prevent them from happening.