Structural highlights
Function
CID_DROME Histone H3-like variant which exclusively replaces conventional H3 in the nucleosome core of centromeric chromatin at the inner plate of the kinetochore (PubMed:11483958, PubMed:16839185). Required for recruitment and assembly of kinetochore proteins, mitotic progression and chromosome segregation (PubMed:24703848, PubMed:11483958, PubMed:16839185). May serve as an epigenetic mark that propagates centromere identity through replication and cell division (PubMed:11483958, PubMed:16839185).[1] [2] [3]
Publication Abstract from PubMed
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.
Structural basis for centromere maintenance by Drosophila CENP-A chaperone CAL1.,Medina-Pritchard B, Lazou V, Zou J, Byron O, Abad MA, Rappsilber J, Heun P, Jeyaprakash AA EMBO J. 2020 Mar 5:e103234. doi: 10.15252/embj.2019103234. PMID:32134144[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Blower MD, Karpen GH. The role of Drosophila CID in kinetochore formation, cell-cycle progression and heterochromatin interactions. Nat Cell Biol. 2001 Aug;3(8):730-9. doi: 10.1038/35087045. PMID:11483958 doi:http://dx.doi.org/10.1038/35087045
- ↑ Blower MD, Daigle T, Kaufman T, Karpen GH. Drosophila CENP-A mutations cause a BubR1-dependent early mitotic delay without normal localization of kinetochore components. PLoS Genet. 2006 Jul;2(7):e110. Epub 2006 Jun 5. PMID:16839185 doi:http://dx.doi.org/05-PLGE-RA-0358R2
- ↑ Mathew V, Pauleau AL, Steffen N, Bergner A, Becker PB, Erhardt S. The histone-fold protein CHRAC14 influences chromatin composition in response to DNA damage. Cell Rep. 2014 Apr 24;7(2):321-330. doi: 10.1016/j.celrep.2014.03.008. Epub 2014 , Apr 3. PMID:24703848 doi:http://dx.doi.org/10.1016/j.celrep.2014.03.008
- ↑ Medina-Pritchard B, Lazou V, Zou J, Byron O, Abad MA, Rappsilber J, Heun P, Jeyaprakash AA. Structural basis for centromere maintenance by Drosophila CENP-A chaperone CAL1. EMBO J. 2020 Mar 5:e103234. doi: 10.15252/embj.2019103234. PMID:32134144 doi:http://dx.doi.org/10.15252/embj.2019103234
