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

• Published in: Cell reports (Cambridge) 2016-03, Vol.14 (8), p.1819-1828
• Main Authors: Lee, Bernard Chi Hang, Lin, Zhongyang, Yuen, Karen Wing Yee
• Format: Article
• Language: English
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2016.01.065

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 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. [Display omitted] •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 Histone H3 variant CENP-A epigenetically marks all functional centromeres, but how it is assembled on holocentromeres is unknown. Lee et al. show that the histone chaperone RbAp46/48LIN-53 is required for CENP-AHCP-3 localization and accurate chromosome segregation in holocentric C. elegans. RbAp46/48LIN-53 may function to escort CENP-AHCP-3 for holocentromere assembly.