Abstract
The centromere is the chromosomal locus essential for chromosome inheritance and genome stability. Human centromeres are located at repetitive alpha satellite DNA arrays that compose approximately 5% of the genome. Contiguous alpha satellite DNA sequence is absent from the assembled reference genome, limiting current understanding of centromere organization and function. Here, we review the progress in centromere genomics spanning the discovery of the sequence to its molecular characterization and the work done during the Human Genome Project era to elucidate alpha satellite structure and sequence variation. We discuss exciting recent advances in alpha satellite sequence assembly that have provided important insight into the abundance and complex organization of this sequence on human chromosomes. In light of these new findings, we offer perspectives for future studies of human centromere assembly and function.
Highlights
The centromere is the chromosomal locus that controls chromosome segregation during cell division
Centromere assembly on the alpha satellite can be enhanced or inhibited, the long-term stability of the human artificial chromosome (HAC) can be monitored by tethering tet repressor (tetR) fluorescent protein fusions, and expression of genes included on the HAC can be tested [39]
Since the discovery of alpha satellite DNA in the late 1970s, the field has moved from identification of centromeric sequences at every human centromere to a basic molecular understanding of the organization and structure of alpha satellite monomers into homogeneous higher order repetitive arrays (Figure 5)
Summary
The centromere is the chromosomal locus that controls chromosome segregation during cell division. The sequence basis of centromere identity is widely debated, since variant centromeres have been identified in humans and other organisms These unusual centromeres include neocentromeres, new centromeres that are formed on unique or non-centromeric DNA sequences [3,4]. Dicentric human chromosomes, those chromosomes that are formed by fusion or translocation, have two regions of centromeric DNA, but often only one is the site of kinetochore formation. Those chromosomes that are formed by fusion or translocation, have two regions of centromeric DNA, but often only one is the site of kinetochore formation In these instances, the alpha satellite DNA appears to be neither necessary nor sufficient for centromere function. We will discuss advances in our understanding of human centromeric DNA, from the discovery of human centromeric sequences through integration of physical and genetic maps of centromeres during the Human Genome Project era to the first centromeric genome assemblies that are only emerging
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