Abstract
All living organisms require accurate mechanisms to faithfully inherit their genetic material during cell division. The centromere is a unique locus on each chromosome that supports a multiprotein structure called the kinetochore. During mitosis, the kinetochore is responsible for connecting chromosomes to spindle microtubules, allowing faithful segregation of the duplicated genome. In most organisms, centromere position and function is not defined by the local DNA sequence context but rather by an epigenetic chromatin-based mechanism. Centromere protein A (CENP-A) is central to this process, as chromatin assembled from this histone H3 variant is essential for assembly of the centromere complex, as well as for its epigenetic maintenance. As a major determinant of centromere function, CENP-A assembly requires tight control, both in its specificity for the centromere and in timing of assembly. In the last few years, there have been several new insights into the molecular mechanism that allow this process to occur. We will review these here and discuss the general implications of the mechanism of cell cycle coupling of centromere inheritance.
Highlights
Cell division requires the coordinate action of mechanisms that duplicate the full complement of the genome and subsequently partition these copies among newly formed daughter cells
Microtubule binding is mediated by the kinetochore, a complex of proteins that is assembled onto the centromere complex during mitosis
Similar to the chromosomal LacO insertions described above, tethering CENP-ACID-LacI fusion protein to the LacO arrays on those plasmids led to the recruitment of centromeric proteins and to microtubule binding. These ectopic centromeres promote stable transmission of the plasmids for multiple cell divisions, even in the absence of the fusion protein that initiated centromere formation. These results provide direct evidence that CENP-A is sufficient to direct centromere formation and can initiate a selfperpetuating epigenetic feedback mechanism that controls centromere identity and stable inheritance (Fig. 2)
Summary
Cell division requires the coordinate action of mechanisms that duplicate the full complement of the genome and subsequently partition these copies among newly formed daughter cells Key to the latter process of chromosome segregation is a chromosomal region called the centromere. This region, initially defined cytologically as the primary constriction on metazoan metaphase chromosomes, is the site of assembly of a large complex of proteins that function in tethering sister chromatids together as well as in generating attachments to spindle microtubules in a bipolar fashion (Fig. 1). Microtubule binding is mediated by the kinetochore, a complex of proteins that is assembled onto the centromere complex during mitosis
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