Centromere

During mitosis in a typical plant or animal cell, each chromosome divides longitudinally into two sister chromosomes that eventually separate and travel to opposite poles of the mitotic spindle. At the beginning of mitosis, when the sister chromosomes have split but are still paired, every chromosome attaches to the spindle at a specific point along its length. That point is referred to as the centromere or spindle attachment region.

Images from an electron microscope show that each sister is attached to fibers emanating from only one pole of the spindle. This allows the sisters to be pulled to opposite poles during mitosis. The electron microscope images also show that the spindle fibers do not terminate on the chromosomes themselves but rather on separate structures, known as kinetochores. Kinetochores are trilaminar bodies that assemble at the centromeres during the early stages of mitosis and disappear after the chromosomes have separated.

The budding yeast Saccharomyces cerevisiae has the simplest known centromeres consisting of a DNA segment only 110 bases in length. The DNA segment in the yeast centromere binds to specific proteins, which, like the kinetochores in higher organisms, link the chromosome to spindle fibers during mitosis. Centromeres of higher plants and animals are much larger, consisting of thousands or millions of bases of DNA and numerous proteins. For reasons that are unknown, centromeres are often flanked by long segments of DNA that do not contain functional genes. These nonfunctional DNA segments, called pericentric heterochromatin, vary in length in different organisms. In some cases they constitute more than half of the whole chromosome.

The crucial role of centromeres in the orderly behavior of chromosomes can be demonstrated by using X rays or other treatments that cause chromosomes to fragment. Pieces of chromosomes that lack centromeres (acentric fragments) do not attach to the spindle and are not pulled to the poles during mitosis. They generally are not included in the nuclei that are newly formed after cell division, and they usually degenerate in the cytoplasm.

Conversely, two fragments that each contain a centromere sometimes fuse, producing a dicentric chromosome. If the two centromeres happen to attach to the same pole at mitosis, the chromosome may move intact to that pole. However, if the centromeres attach to opposite poles, the chromosome will be stretched during mitosis and will eventually break. In general, therefore, only chromosomes with one centromere are stable.

Some organisms, including hemipteran insects and nematode worms, have holocentric or holokinetic chromosomes. In these organisms, spindle fibers attach all along one side of each sister chromosome, and the chromosomes are pulled more or less sideways to the pole.

Centromeres also play an important role during meiosis, in which the number of chromosomes is halved. The first meiotic division differs from a typical mitotic division in two respects:

1. In the first meiotic division, chromosomes derived from the organism's maternal and paternal parents pair at the beginning of meiosis. As ina typical mitosis, each of these chromosomes has split into two sisters, so after pairing there are four chromosomes in a group. The kinetochore is a protein structure that forms at the centromere before mitosis. Microtubules attach to it, and pull apart the two chromatids (not shown to scale). Adapted from <http://www.sus.mcgill.ca/bio202/00b/lec2/sld028.htm> and <http://www.esb.utexas.edu/dr325/Supplements/kinetchr.htm>.
2. When these four chromosomes attach to the spindle, sister chromosomes attach to the same pole, not to opposite poles as occurs in mitosis.

As a result, both maternal chromosomes move to one pole, while both paternal chromosomes move to the opposite pole. It is this unique behavior of the centromeres at meiosis that accounts for the separation of maternal and paternal genes during formation of sperm and eggs, which in turn is the basis of Mendelian genetics.