Centromeres: the missing link in the development of human artificial chromosomes

Abstract

Successful construction of artificial chromosomes is an important step for studies to elucidate the DNA elements necessary for chromosome structure and function. A roadblock to developing a tractable system in multicellular organisms, including humans, is the poorly understood nature of centromeres. Progress, has been made in defining the satellite DNA that appears to contribute to the centromere in both humans and Drosophila and large arrays of alpha satellite DNA have been used to construct first-generation human artificial chromosomes. Non-satellite DNA sequences are also capable of forming 'neo-centromeres' under some circumstances, however, raising questions about the sequence-dependence of centromere and kinetochore assembly. Taken together with new information on the nature of protein components of the kinetochore, these data support a model in which functional kinetochores are assembled on centromeric chromatin, the competence of which is established epigenetically. The development of human artificial chromosome systems should facilitate investigation of the DNA and chromatin requirements for active centromere assembly.