Identification of bridgin, an unconventional linker, connects the outer kinetochore to centromeric chromatin

ABSTRACT The microtubule-binding outer kinetochore is linked to centromeric chromatin through the inner kinetochore CENP-C Mif2 , CENP-T Cnn1 , and CENP-U Ame1 pathways. These are the only known kinetochore linker proteins across eukaryotes. Linker proteins are structurally less conserved than their outer kinetochore counterparts. Here, we demonstrate the recurrent loss of most inner kinetochore CCAN, including certain linker proteins during evolution in the fungal phylum of Basidiomycota. By studying the kinetochore interactome, a previously undescribed linker protein, bridgin was identified in the basidiomycete Cryptococcus neoformans , a human fungal pathogen . In vivo and in vitro functional analyses of bridgin reveal that it binds to the outer kinetochore and centromere chromatin simultaneously to ensure accurate kinetochore-microtubule attachments. Unlike known linker proteins, bridgin is recruited by the outer kinetochore. Homologs of bridgin were identified outside fungi. These results showcase a divergent strategy, with a more ancient origin than fungi, to link the outer kinetochore to centromeric chromatin.