neocentromeres

A neocentromere is a functional centromere that forms at a chromosomal location where no centromere function existed previously. Unlike canonical centromeres, which are typically defined by clusters of alpha-satellite DNA, neocentromeres arise largely through epigenetic mechanisms that establish centromeric chromatin and kinetochore assembly at a new site. They are capable of guiding proper chromosome segregation during cell division.

Formation of neocentromeres involves the deposition of the centromere-specific histone variant CENP-A and the subsequent recruitment of kinetochore proteins, including CENP-C and components of the Ndc80 complex, which connect the chromosome to spindle microtubules. While many centromeres rely on repetitive DNA, neocentromeres can operate without such sequences, illustrating the epigenetic nature of centromere identity. Most neocentromeres establish and maintain their function over multiple cell generations, though their stability can vary and some may be prone to inactivation.

Neocentromeres have been observed in various organisms, including humans, where they often arise after chromosomal rearrangements that eliminate or inactivate the native centromere. Clinically, they are associated with certain chromosomal abnormalities and developmental disorders, but carriers can also be phenotypically normal. The study of neocentromeres sheds light on how centromeres are specified independently of DNA sequence, informs our understanding of chromosome stability and evolution, and provides a system to explore kinetochore assembly in noncanonical genomic contexts.