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Structural basis for centromere maintenance by Drosophila CENP ‐A chaperone CAL 1
Author(s) -
MedinaPritchard Bethan,
Lazou Vasiliki,
Zou Juan,
Byron Olwyn,
Abad Maria A,
Rappsilber Juri,
Heun Patrick,
Jeyaprakash A Arockia
Publication year - 2020
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.2019103234
Subject(s) - centromere , biology , microbiology and biotechnology , chaperone (clinical) , nucleosome , chromosome segregation , genetics , histone , chromosome , gene , medicine , pathology
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 CAL 1, 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 CAL 1 fragment wraps around CENP ‐A/H4 through multiple physical contacts, a C‐terminal CAL 1 fragment directly binds a CENP ‐C cupin domain dimer. Although divergent at the primary structure level, CAL 1 thus binds CENP ‐A/H4 using evolutionarily conserved and adaptive structural principles. The CAL 1 binding site on CENP ‐C is strategically positioned near the cupin dimerisation interface, restricting binding to just one CAL 1 molecule per CENP ‐C dimer. Overall, by demonstrating how CAL 1 binds CENP ‐A/H4 and CENP ‐C, we provide key insights into the minimalistic principles underlying centromere maintenance.