RbAp46/48LIN-53 Is Required for Holocentromere Assembly in Caenorhabditis elegans

RbAp46/48LIN-53 Is Required for Holocentromere Assembly in Caenorhabditis elegans

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Centromeres, the specialized chromosomal regions for recruiting kinetochores and directing chromosome segregation, are epigenetically marked by a centromeric histone H3 variant, CENP-A.To maintain centromere identity through cell cycles, CENP-A diluted during DNA replication is replenished.The licensing factor M18BP1KNL-2 is Box known to recruit CENP-A to holocentromeres.Here, we show that RbAp46/48LIN-53, a conserved histone chaperone, is required for CENP-AHCP-3 localization in holocentric Caenorhabditis elegans.Indeed, RbAp46/48LIN-53 and CENP-AHCP-3 localizations are interdependent.

RbAp46/48LIN-53 localizes to the centromere during metaphase in a CENP-AHCP-3- and M18BP1KNL-2-dependent manner, suggesting CENP-AHCP-3 loading may occur before Lubes and Lotions anaphase.RbAp46/48LIN-53 does not function at the centromere through histone acetylation, H3K27 trimethylation, or its known chromatin-modifying complexes.RbAp46/48LIN-53 may function independently to escort CENP-AHCP-3 for holocentromere assembly but is dispensable for other kinetochore protein recruitment.Nonetheless, depletion of RbAp46/48LIN-53 leads to anaphase bridges and chromosome missegregation.This study unravels the holocentromere assembly hierarchy and its conservation with monocentromeres.