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

Shreyas Sridhar, Tetsuya Hori, Reiko Nakagawa, Tatsuo Fukagawa and Kaustuv Sanyal

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Oct 23, 2019
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Received Date: 2nd October 19

The microtubule-binding outer kinetochore is linked to centromeric chromatin through the inner kinetochore CENP-CMif2, CENP-TCnn1, and CENP-QAme1 pathways. These are the only known kinetochore linker proteins across eukaryotes. Linker proteins are structurally less conserved than their outer kinetochore counterparts. In this study, 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 novel 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 DNA 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 an alternate and novel strategy, with a more ancient origin than fungi, to link the outer kinetochore to centromeric chromatin.

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This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.

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