centromeres

Centromere is the region of a chromosome responsible for its proper segregation during cell division. It is the site where kinetochores assemble and where sister chromatids remain most tightly held until anaphase. In most eukaryotes the centromere lies at a defined position on each chromosome, forming the primary constriction visible under light microscopy in metaphase spreads. Some species are holocentric, with kinetochores distributed along the length of the chromosome.

Structure and identity: Centromeres are defined by epigenetic features rather than DNA sequence in many organisms. The centromeric chromatin contains nucleosomes that include the histone H3 variant CENP-A, which helps specify centromere identity and kinetochore assembly. Surrounding pericentromeric regions are rich in repetitive DNA and heterochromatin, contributing to cohesion and proper chromosome folding. In humans, constitutive centromeric DNA comprises alpha-satellite repeats, but centromere function does not strictly depend on a particular sequence, and new centromeres (neocentromeres) can form at non-traditional locations.

Function: The kinetochore is a multiprotein complex that assembles at the centromere and attaches chromosomes to spindle microtubules. Cohesin maintains sister-chromatid cohesion up to anaphase. Microtubule dynamics drive chromosome movement, while tension across sister centromeres ensures proper bi-orientation.

Evolution and clinical relevance: Centromeres are rapidly evolving in sequence between species, yet function is conserved. Centromere malfunctions can cause aneuploidy and chromosomal instability, features common in cancers and some congenital disorders. Neocentromere formation and centromere repositioning illustrate how centromere identity can shift without altering overall chromosome structure.