Centromere

Chromosome

Centromere Placement

Human karyotype with bands and sub-bands

Centromere is a region on a chromosome where the two sister chromatids are joined together during the cell cycle. The centromere plays a crucial role in cell division, particularly during mitosis and meiosis, by ensuring the accurate distribution of chromosomes to daughter cells. It is also the attachment site for kinetochore proteins, which connect the chromosomes to the microtubules of the mitotic spindle.

Structure

The structure of the centromere varies among different species. In most eukaryotes, the centromere is characterized by a distinct region of DNA sequence that is rich in base pairs of adenine (A) and thymine (T), known as satellite DNA. This DNA is tightly packed and forms a specialized type of chromatin called heterochromatin. The specific DNA sequences within centromeres are critical for the binding of centromere-specific proteins, including the centromere protein A (CENP-A), which is essential for the assembly of the kinetochore complex.

Function

The primary function of the centromere is to ensure the correct segregation of chromosomes during cell division. During mitosis and meiosis, the chromosomes are duplicated, and each copy is pulled to opposite poles of the dividing cell. The centromere serves as the pivotal point for this movement, with kinetochores attaching to the microtubules of the spindle apparatus. This attachment allows the chromosomes to be aligned at the metaphase plate and subsequently segregated accurately to ensure that each daughter cell receives the correct number of chromosomes.

Centromere Position

Centromeres can be classified based on their position on the chromosome:

• Metacentric: The centromere is located near the middle of the chromosome, resulting in two arms of equal length.
• Submetacentric: The centromere is off-center, creating one long arm and one short arm.
• Acrocentric: The centromere is situated close to one end of the chromosome, leaving one very long arm and a satellite-bearing short arm.
• Telocentric: The centromere is at the very end of the chromosome, effectively creating a single arm.

Evolution

The evolution of centromeres has been a subject of interest, as they show a high degree of diversity across different species. Despite this diversity, the fundamental role of centromeres in chromosome segregation is conserved. The variation in centromere DNA sequences and the proteins that bind to these sequences suggest a co-evolutionary relationship between centromere DNA and centromere-specific proteins.

Clinical Significance

Abnormalities in centromere structure or function can lead to improper chromosome segregation, which is a hallmark of many genetic disorders and diseases, including cancer. For example, mutations in centromere proteins or misregulation of centromere function can result in aneuploidy, a condition characterized by an abnormal number of chromosomes, which is associated with developmental disorders and tumorigenesis.