Bridgin connects the outer kinetochore to centromeric chromatin

Shreyas Sridhar, Tetsuya Hori, Reiko Nakagawa, Tatsuo Fukagawa () and Kaustuv Sanyal ()
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Shreyas Sridhar: Molecular Biology and Genetics Unit, Jawaharlal Nehru Center for Advanced Scientific Research (JNCASR)
Tetsuya Hori: Graduate School of Frontier Biosciences, Osaka University
Reiko Nakagawa: RIKEN Center for Biosystems Dynamics Research (BDR)
Tatsuo Fukagawa: Graduate School of Frontier Biosciences, Osaka University
Kaustuv Sanyal: Molecular Biology and Genetics Unit, Jawaharlal Nehru Center for Advanced Scientific Research (JNCASR)

Nature Communications, 2021, vol. 12, issue 1, 1-19

Abstract: Abstract The microtubule-binding outer kinetochore is coupled to centromeric chromatin through CENP-CMif2, CENP-TCnn1, and CENP-UAme1 linker pathways originating from the constitutive centromere associated network (CCAN) of the inner kinetochore. Here, we demonstrate the recurrent loss of most CCAN components, including certain kinetochore linkers during the evolution of the fungal phylum of Basidiomycota. By kinetochore interactome analyses in a model basidiomycete and human pathogen Cryptococcus neoformans, a forkhead-associated domain containing protein “bridgin” was identified as a kinetochore component along with other predicted kinetochore proteins. In vivo and in vitro functional analyses of bridgin reveal its ability to connect the outer kinetochore with centromeric chromatin to ensure accurate chromosome segregation. Unlike established CCAN-based linkers, bridgin is recruited at the outer kinetochore establishing its role as a distinct family of kinetochore proteins. Presence of bridgin homologs in non-fungal lineages suggests an ancient divergent strategy exists to bridge the outer kinetochore with centromeric chromatin.

Date: 2021
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DOI: 10.1038/s41467-020-20161-9

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