Each normal human chromosome has a single centromere, which appears as a constriction when viewed under the microscope. The centromere can be near the middle of the chromosome or near one end. It partitions the chromosome into long and short arms (see Figure 1).
The centromere is required for proper chromosome segregation. Every time a cell divides, the chromosomes first replicate so there are two identical copies (sister chromatids) and then line up across the middle of the cell. The chromatids are segregated so that each daughter cell receives one copy.
Segregation is achieved by building a cage-like structure called the spindle across the cell's nucleus. This attaches to the aligned chromosomes and draws sister chromatids to opposite poles of the dividing cell (see Figure 2). The spindle fibres attach to protein complexes called kinetochores that assemble on the centromere of each chromosome.
What are the DNA sequences that define a centromere? Human centromeres are large (several million base pairs) and consist predominantly of the same 171-bp sequence, known α-satellite DNA, repeated hundreds of thousands of times. This structure is recognised by the components of the kinetochore.
Chromosome derivatives with no centromere or multiple centromeres are occasionally formed when normal chromosomes are broken and incorrectly repaired. These aberrant structures are important because they do not segregate properly and are often lost from the dividing cell. If this happens in the germ cells, the resulting eggs or sperm can be unbalanced (have extra or missing chromosomes or chromosome segments). Many embryos formed from unbalanced gametes are spontaneously aborted but some survive to term producing individuals with birth defects such as Down syndrome.