Centromere

  The centromere is a region in the middle of the chromosome involved in cell division and the control of gene expression.

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Function

The centromere is the strongest and thinnest region of the chromosome. It holds together the two similar halves of the chromosome, the sister chromatids. During cell division, the spindle fibers pull the chromatids apart. Each chromatid has its own centromere, and the spindle fibers attach to the kinetochore site. The centromere looks like a constriction along the length of the chromosome.

A centromere functions in sister chromatid adhesion, kinetochore formation, and pairing of homologous chromosomes.

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.

When the centromere doesn't function properly, the chromosomes don't align and separate properly, resulting in the wrong number of chromosomes in the daughter cells (aneuploidy), and conditions such as Down syndrome, if the cells survive at all.

Centromere Positions

Each chromosome has two arms, labeled p (the shorter of the two) and q (the longer). They can be connected in either metacentric, submetacentric, acrocentric or telocentric manner. (While the p arm is named for petite meaning small, the q arm is named thus simply because it follows p in the alphabet.)

Metacentric

If both arms are equal in length, the chromosome is said to be metacentric. Robertsonian -- fusion of 2 p arms by centric fusion to form metacentric chromosome.

Submetacentric

If arms' lengths are unequal, the chromosome is said to be submetacentric

Acrocentric

If the p (short) arm is so short that is hard to observe, but still present, then the chromosome is acrocentric (The "acro-" in acrocentric refers to the Greek word for "peak.").

There are five acrocentric chromosomes in the human genome: 13, 14, 15, 21 and 22. These five chromosomes are the site of genes encoding rRNAs.

Telocentric

A telocentric chromosome's centromere is located at the terminal end of the chromosome. Telomeres may extend from both ends of the chromosome. All mouse chromosomes are telocentric^[1]; humans do not possess any telocentric chromosomes.

The centromeric sequence

In most eukaryotes, the centromere has no defined DNA sequence. It typically consists of large arrays of repetitive DNA (e.g. 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 125 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 essential for the recruitment of the cohesin complex that mediates sister chromatid cohesion after DNA replication as well as coordinating sister chromatid separation during anaphase. In this chromatin, the normal histone H3 is replaced with a centromere-specific variant, CENP-A in humans (Lodish et al. 2004). The presence of CENP-A is believed to be important for the assembly of the kinetochore on the centromere. CENP-C has been shown to localise almost exclusively to these regions of CENP-A associated chromatin.

In the yeast Schizosaccharomyces pombe (and probably in other eukaryotes), the formation of centromeric heterochromatin is connected to RNAi.^[2] 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.

Centromere proteins are also the autoantigenic target for some anti-nuclear antibodies such as anti-centromere antibodies

Related links

• Monopolin
• Genetics
• Cell biology

References

Further reading

• Lodish et al.; Molecular Cell Biology; fifth edition; 2004; ISBN 0716743663