Article Metrics


Online attention

Structural basis for centromere maintenance by Drosophila CENP ‐A chaperone CAL 1

DOI: 10.15252/embj.2019103234 DOI Help

Authors: Bethan Medina-Pritchard (University of Edinburgh) , Vasiliki Lazou (University of Edinburgh) , Juan Zou (University of Edinburgh) , Olwyn Byron (University of Glasgow) , Maria A. Abad (University of Edinburgh) , Juri Rappsilber (University of Edinburgh; Technische Universität Berlin) , Patrick Heun (University of Edinburgh) , A. Arockia Jeyaprakash (University of Edinburgh)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: The Embo Journal , VOL 7

State: Published (Approved)
Published: March 2020

Open Access Open Access

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.

Subject Areas: Biology and Bio-materials

Instruments: I03-Macromolecular Crystallography , I04-1-Macromolecular Crystallography (fixed wavelength)

Added On: 01/04/2020 11:31


Discipline Tags:

Genetics Structural biology Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)