Arabidopsis MZT1 homologs GIP1 and GIP2 are essential for centromere architecture

Centromeres play a pivotal role in maintaining genome integrity by facilitating the recruitment of kinetochore and sister-chromatid cohesion proteins, both required for correct chromosome segregation. Centromeres are epigenetically specified by the presence of the histone H3 variant (CENH3). In this...

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Published in:Proceedings of the National Academy of Sciences - PNAS Vol. 112; no. 28; pp. 8656 - 8660
Main Authors: Batzenschlager, Morgane, Inna Lermontova, Veit Schubert, Jörg Fuchs, Alexandre Berr, Maria A. Koini, Guy HoulnöeÌ, Etienne Herzog, Twan Rutten, Abdelmalek Alioua, Paul Fransz, Anne-Catherine Schmit, Marie-Edith ChaboutöéeÌ
Format: Journal Article
Language:English
Published: United States National Academy of Sciences 14-07-2015
National Acad Sciences
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Summary:Centromeres play a pivotal role in maintaining genome integrity by facilitating the recruitment of kinetochore and sister-chromatid cohesion proteins, both required for correct chromosome segregation. Centromeres are epigenetically specified by the presence of the histone H3 variant (CENH3). In this study, we investigate the role of the highly conserved γ-tubulin complex protein 3-interacting proteins (GIPs) in Arabidopsis centromere regulation. We show that GIPs form a complex with CENH3 in cycling cells. GIP depletion in the gip1gip2 knockdown mutant leads to a decreased CENH3 level at centromeres, despite a higher level of Mis18BP1/KNL2 present at both centromeric and ectopic sites. We thus postulate that GIPs are required to ensure CENH3 deposition and/or maintenance at centromeres. In addition, the recruitment at the centromere of other proteins such as the CENP-C kinetochore component and the cohesin subunit SMC3 is impaired in gip1gip2 . These defects in centromere architecture result in aneuploidy due to severely altered centromeric cohesion. Altogether, we ascribe a central function to GIPs for the proper recruitment and/or stabilization of centromeric proteins essential in the specification of the centromere identity, as well as for centromeric cohesion in somatic cells. Centromeres are crucial as they avoid genomic instability during mitosis, but the mechanisms involved in their assembly and maintenance are not yet fully elucidated in eukaryotes. Here, we describe a previously unidentified aspect of centromere regulation mediated by γ-tubulin complex protein 3-interacting proteins (GIPs). Our data correlate centromere assembly and cohesion through the recruitment of specific protein complexes in the nucleus. Due to the conservation of GIPs/mitotic spindle organizing protein 1 among fungi, mammals, and plants, our results open a new field of investigation for centromere regulation.
Bibliography:http://dx.doi.org/10.1073/pnas.1506351112
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PMCID: PMC4507256
Edited by James A. Birchler, University of Missouri, Columbia, MO, and approved May 12, 2015 (received for review April 2, 2015)
Author contributions: A.-C.S. and M.-E.C. designed research; M.B., V.S., J.F., M.A.K., G.H., E.H., T.R., A.A., A.-C.S., and M.-E.C. performed research; I.L., G.H., and M.-E.C. contributed new reagents/analytic tools; M.B., I.L., V.S., J.F., A.B., M.A.K., G.H., E.H., P.F., A.-C.S., and M.-E.C. analyzed data; A.B., P.F., A.-C.S., and M.-E.C. wrote the paper; and M.-E.C. is the coordinator of the collaborative project.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1506351112