CENP-A Ubiquitylation Contributes to Maintaining the Chromosomal Location of the Centromere

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.

Keywords

• CENP-A
• centromere identity
• centromere
• CUL4A-RBX1- COPS8 E3 ligase
• dimerization
• epigenetics
• kinetochore
• lysine 124 (K124), neocentromere
• ubiquitylation