Centromere

Structure and proteins

Centromeres are defined by a combination of DNA sequence and specialized chromatin. Many organisms have arrays of repetitive DNA, often called centromeric DNA or satellite sequences, but sequence alone does not fully determine centromere function. A hallmark feature is the replacement of canonical histone H3 by a variant called CENP-A, which helps nucleate a protein complex known as the kinetochore. Multiple centromere proteins (CENPs) and associated factors assemble on this chromatin to connect chromosomes to microtubules.

Function during cell division

At the centromeric constriction the kinetochore forms and attaches microtubules, allowing tension to be sensed and correct bi-orientation to be achieved. Cohesin proteins maintain sister chromatid cohesion around the centromere until anaphase, when separase triggers separation. Proper centromere function is essential to prevent mis-segregation and aneuploidy, a feature of many cancers and developmental disorders.

Types and variation

Centromeres vary between species. Some yeasts have small, sequence-specific "point" centromeres; most animals and plants have larger regional centromeres defined epigenetically by CENP-A and repetitive DNA. A few organisms are holocentric, distributing centromeric activity along the entire length of the chromosome. This diversity reflects differing evolutionary pressures on centromere sequences and associated proteins.

Importance in research and medicine

• Errors in centromere or kinetochore function contribute to chromosome instability and disease.
• Centromeric sequences and proteins are targets for studies of chromosome evolution and speciation.
• Synthetic or engineered centromeres are used to build artificial chromosomes for gene delivery and functional studies.

Notable facts

Although repetitive DNA is common at centromeres, the position of the functional centromere is often maintained epigenetically rather than strictly by sequence. Centromere-associated proteins evolve rapidly in some lineages, which can drive incompatibilities between closely related species. For further background and visual guides, see introductory resources on chromosomes and reviews on centromere biology (sister chromatids, spindle, mitosis, centromeric DNA, satellite sequences, centromere proteins).