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Detrimental incorporation of excess Cenp-A/Cid and Cenp-C into Drosophila centromeres is prevented by limiting amounts of the bridging factor Cal1

Title data

Schittenhelm, Ralf B. ; Althoff, Friederike ; Heidmann, Stefan ; Lehner, Christian F.:
Detrimental incorporation of excess Cenp-A/Cid and Cenp-C into Drosophila centromeres is prevented by limiting amounts of the bridging factor Cal1.
In: Journal of Cell Science. Vol. 123 (November 2010) Issue 21 . - pp. 3768-3779.
ISSN 1477-9137
DOI: https://doi.org/10.1242/jcs.067934

Project information

Project financing: Deutsche Forschungsgemeinschaft

Abstract in another language

Propagation of centromere identity during cell cycle progression in higher eukaryotes depends critically on the faithful incorporation of a centromere-specific histone H3 variant encoded by CENPA in humans and cid in Drosophila. Cenp-A/Cid is required for the recruitment of Cenp-C, another conserved centromere protein. With yeast three-hybrid experiments, we demonstrate that the essential Drosophila centromere protein Cal1 can link Cenp-A/Cid and Cenp-C. Cenp-A/Cid and Cenp-C interact with the N- and C-terminal domains of Cal1, respectively. These Cal1 domains are sufficient for centromere localization and function, but only when linked together. Using quantitative in vivo imaging to determine protein copy numbers at centromeres and kinetochores, we demonstrate that centromeric Cal1 levels are far lower than those of Cenp-A/Cid, Cenp-C and other conserved kinetochore components, which scale well with the number of kinetochore microtubules when comparing Drosophila with budding yeast. Rather than providing a stoichiometric link within the mitotic kinetochore, Cal1 limits centromeric deposition of Cenp-A/Cid and Cenp-C during exit from mitosis. We demonstrate that the low amount of endogenous Cal1 prevents centromere expansion and mitotic kinetochore failure when Cenp-A/Cid and Cenp-C are present in excess.

Further data

Item Type: Article in a journal
Refereed: Yes
Keywords: Centromere; Kinetochore; Mitosis; Chromosome instability; Cal1
Histone H3 Variant; Fission Yeast SCM3; DNA-Binding; Molecular Architecture; Protein Network; Kinetochore; Chromatin; Domains; Localization; Organization
Institutions of the University: Faculties
Faculties > Faculty of Biology, Chemistry and Earth Sciences
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Biology
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Biology > Chair Genetics
Result of work at the UBT: No
DDC Subjects: 500 Science
500 Science > 570 Life sciences, biology
Date Deposited: 05 Mar 2020 09:54
Last Modified: 05 Mar 2020 09:54
URI: https://eref.uni-bayreuth.de/id/eprint/54467