Abstract
The centromere plays an essential role in accurate chromosome segregation, and the chromosomal location of the centromere is determined by the presence of a histone H3 variant, centromere protein A (CENP-A), in centromeric nucleosomes. However, the precise mechanisms of deposition, maintenance, and inheritance of CENP-A at centromeres are unclear. We have reported that CENP-A deposition requires ubiquitylation of CENP-A lysine 124 mediated by the E3 ligase activity of Cullin 4A (CUL4A)—RING-box protein 1 (RBX1)—COP9 signalsome complex subunit 8 (COPS8). We have proposed a model of inheritance for CENP-A ubiquitylation, through dimerization between rounds of cell divisions, that maintains the position of centromeres.
Highlights
During cell division, proper chromosomal segregation must be achieved; otherwise chromosomes may be unequally distributed among daughter cells
Centromere identity is defined in an epigenetic manner by the presence of a special nucleosome that contains a centromere-specific histone H3 variant, centromere protein A (CENP-A)
Suggest that the heterodimer is presumably we suggest that the heterodimer is presumably recognized by the Cullin 4A (CUL4A) complex, and the new CENP-A is ubiquitylated and maintained at the recognized by the CUL4A complex, and the new CENP-A is ubiquitylated and maintained at the centromeres [3]
Summary
Proper chromosomal segregation must be achieved; otherwise chromosomes may be unequally distributed among daughter cells. The major role of the centromere is to provide sites for the kinetochore, the protein complexes that bind microtubules of the spindle bundle during cell division. The temporal-spatial regulation and structures of centromere and kinetochore proteins are important keys to understand chromosome instability (CIN) that results in aneuploidy (i.e., an incorrect number of chromosomes). There are several fundamental questions to be solved: What mechanism determines the specific chromosomal location of the functional centromere (i.e., centromere identity)? Centromere identity is defined in an epigenetic manner by the presence of a special nucleosome that contains a centromere-specific histone H3 variant, centromere protein A (CENP-A). Proper deposition of CENP-A at the centromere is required for proper centromere function, and this is a fundamental biological. CENP-A (a.k.a., nucleosomes) localize to the inner kinetochores
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