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

• RbAp46/48LIN-53 is crucial for chromosome segregation in holocentric C. elegans
• RbAp46/48LIN-53 localizes to centromeres in metaphase and disappears in anaphase
• RbAp46/48LIN-53 localizes and stabilizes CENP-AHCP-3 for holocentromere assembly
• RbAp46/48LIN-53’s centromeric role is not due to histone acetylation or methylation

SummaryCentromeres, 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 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 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.

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