Structural basis for centromere maintenance by Drosophila CENP-A chaperone CAL1

Medina-Pritchard, B., Lazou, V., Zuo, J., Byron, O. , Abad, M. A., Rappsilber, J., Heun, P. and Jeyaprakash, A. A. (2020) Structural basis for centromere maintenance by Drosophila CENP-A chaperone CAL1. EMBO Journal, 39(7), e103234. (doi: 10.15252/embj.2019103234) (PMID:32134144) (PMCID:PMC7110144)

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Abstract

Centromeres are microtubule attachment sites on chromosomes defined by the enrichment of histone variant CENP‐A‐containing nucleosomes. To preserve centromere identity, CENP‐A must be escorted to centromeres by a CENP‐A‐specific chaperone for deposition. Despite this essential requirement, many eukaryotes differ in the composition of players involved in centromere maintenance, highlighting the plasticity of this process. In humans, CENP‐A recognition and centromere targeting are achieved by HJURP and the Mis18 complex, respectively. Using X‐ray crystallography, we here show how Drosophila CAL1, an evolutionarily distinct CENP‐A histone chaperone, binds both CENP‐A and the centromere receptor CENP‐C without the requirement for the Mis18 complex. While an N‐terminal CAL1 fragment wraps around CENP‐A/H4 through multiple physical contacts, a C‐terminal CAL1 fragment directly binds a CENP‐C cupin domain dimer. Although divergent at the primary structure level, CAL1 thus binds CENP‐A/H4 using evolutionarily conserved and adaptive structural principles. The CAL1 binding site on CENP‐C is strategically positioned near the cupin dimerisation interface, restricting binding to just one CAL1 molecule per CENP‐C dimer. Overall, by demonstrating how CAL1 binds CENP‐A/H4 and CENP‐C, we provide key insights into the minimalistic principles underlying centromere maintenance.

Item Type:Articles
Additional Information:The Wellcome Trust generously supported this work through a Wellcome Trust Career Development Grant (095822) and a Senior Research Fellowship (202811) to AAJ, a Senior Research Fellowship (084229) to JR, a Senior Research Fellowship (103897) to PH, a Centre Core Grant (092076 and 203149) and an instrument grant (091020) to the Wellcome Trust Centre for Cell Biology, a Multi‐User Equipment grant 101527/Z/13/Z to the EPPF and a Wellcome‐UoE ISSF award towards the procurement of SEC‐MALS equipment for the EPPF. PH was further supported by a European Research Council Starting‐Consolidator Grant (311674–BioSynCEN).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Byron, Professor Olwyn
Authors: Medina-Pritchard, B., Lazou, V., Zuo, J., Byron, O., Abad, M. A., Rappsilber, J., Heun, P., and Jeyaprakash, A. A.
Subjects:Q Science > QH Natural history > QH345 Biochemistry
College/School:College of Medical Veterinary and Life Sciences > School of Life Sciences
Journal Name:EMBO Journal
Journal Abbr.:EMBO J.
Publisher:EMBO Press
ISSN:0261-4189
ISSN (Online):1460-2075
Published Online:05 March 2020
Copyright Holders:Copyright © 2020 The Authors
First Published:First published in EMBO Journal 39(7): e103234
Publisher Policy:Reproduced under a Creative Commons License

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