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EMBO J. 2020 Mar 5:e103234. doi: 10.15252/embj.2019103234. [Epub ahead of print]

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

Author information

1
Wellcome Centre for Cell Biology, University of Edinburgh, Edinburgh, UK.
2
School of Life Sciences, University of Glasgow, Glasgow, UK.
3
Institute of Biotechnology, Technische Universität Berlin, Berlin, Germany.

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.

KEYWORDS:

CAL1; CENP-A; CENP-C; centromeres; chromosome segregation

PMID:
32134144
DOI:
10.15252/embj.2019103234

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