Centromere

The centromere is a region on chromosomes with a special sequence and structure. The centromere plays a role in cellular division and the control of gene expression.

Function
A centromere functions in sister chromatid adhesion, kinetochore formation, pairing of homologous chromosomes and is involved in the control of gene expression.

A centromere is the region where sister chromatids join in the double chromosomal structure during mitosis, prophase and metaphase. The centromere is also where kinetochore formation takes place: proteins bind on the centromeres that form an anchor point for the spindle formation required for the pull of chromosomes toward the centrioles during the anaphase and telophase of mitosis.

Aberrant centromeric function can lead to improper chromosomal alignment and segregation, resulting in aneuploidy and conditions such as Down syndrome.

The centromeric sequence
In most eukaryotes, the centromere has no defined DNA sequence. It typically consists of large arrays of repetitive DNA (eg, satellite DNA) where the sequence within individual repeat elements is similar but not identical. In humans, the primary centromeric repeat unit is called α-satellite (or alphoid), although a number of other sequence types are found in this region. However, in budding yeasts the centromere region is relatively small (about 200 bp DNA) and contains two highly conserved DNA sequences that serve as binding sites for essential kinetochore proteins.

Inheritance
Epigenetic inheritance plays a major role in specifying the centromere in most organisms. The daughter chromosomes will assemble centromeres in the same place as the parent chromosome, independent of sequence. However, there must still be some original way in which the centromere is specified, even if it is subsequently propagated epigenetically.

Structure
The centromeric DNA is normally in a heterochromatin state, which is probably essential for its function. In this chromatin, the normal histone H3 is replaced with CENP-A, a centromere-specific variant (in S. cerevisiae, but similar specialized nucleosomes seem to be present in all eucaryotic cells). The presence of CENP-A is believed to be important for the assembly of the kinetochore on the centromere and may play a role in the epigenetic inheritance of the centromere site.

In the yeast Schizosaccharomyces pombe (and probably in other eukaryotes), the formation of centromeric heterochromatin is connected to RNAi*. In nematodes such as Caenorhabditis elegans, some plants, and the insect orders Lepidoptera and Hemiptera, chromosomes are "holocentric", indicating that there is not a primary site of microtubule attachments or a primary constriction, and a "diffuse" kinetochore assembles along the entire length of the chromosome.

Centromeric aberrations
In rare cases in humans, neocentromeres can form at new sites on the chromosome. This must be coupled with the inactivation of the previous centromere since chromosomes with two functional centromeres (Dicentric chromosome) will result in chromosome breakage during mitosis. In some unusual cases human neocentromeres have been observed to form spontaneously on fragmented chromosomes. Some of these new positions were originally euchromatic and lack alpha satellite DNA altogether.

Related links

 * Genetics
 * Cell biology