The role of centromeric repeats and transcripts in kinetochore assembly and function

Centromeres are the chromosomal domains, where the kinetochore protein complex is formed, mediating proper segregation of chromosomes during cell division. Although the function of centromeres has remained conserved during evolution, centromeric DNA is highly variable, even in closely related species. In addition, the composition of the kinetochore complexes varies among organisms. Therefore, it is assumed that the centromeric position is determined epigenetically, and the centromeric histone H3 (CENH3) serves as an epigenetic marker. The loading of CENH3 onto centromeres depends on centromere-licensing factors, chaperones, and transcription of centromeric repeats. Several proteins that regulate CENH3 loading and kinetochore assembly interact with the centromeric transcripts and DNA in a sequence-independent manner. However, the functional aspects of these interactions are not fully understood. This review discusses the variability of centromeric sequences in different organisms and the regulation of their transcription through the RNA Pol II and RNAi machinery. The data suggest that the interaction of proteins involved in CENH3 loading and kinetochore assembly with centromeric DNA and transcripts plays a role in centromere, and possibly neocentromere, formation in a sequence-independent manner.