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Differential role of CENP-A in the segregation of holocentric C. elegans chromosomes during meiosis and mitosis

Nature Cell Biology volume 7, pages 1248–1255 (2005)Cite this article

An Erratum to this article was published on 02 December 2005

Abstract

Two distinct chromosome architectures are prevalent among eukaryotes: monocentric, in which localized centromeres restrict kinetochore assembly to a single chromosomal site, and holocentric, in which diffuse kinetochores form along the entire chromosome length. During mitosis, both chromosome types use specialized chromatin, containing the histone H3 variant CENP-A1,2,3, to direct kinetochore assembly4,5,6,7. For the segregation of recombined homologous chromosomes during meiosis8,9, monocentricity is thought to be crucial for limiting spindle-based forces to one side of a crossover and to prevent recombined chromatids from being simultaneously pulled towards both spindle poles. The mechanisms that allow holocentric chromosomes to avert this fate remain uncharacterized. Here, we show that markedly different mechanisms segregate holocentric chromosomes during meiosis and mitosis in the nematode Caenorhabditis elegans. Immediately prior to oocyte meiotic segregation, outer-kinetochore proteins were recruited to cup-like structures on the chromosome surface via a mechanism that is independent of CENP-A. In striking contrast to mitosis, both oocyte meiotic divisions proceeded normally following depletion of either CENP-A or the closely associated centromeric protein CENP-C. These findings highlight a pronounced difference between the segregation of holocentric chromosomes during meiosis and mitosis and demonstrate the potential to uncouple assembly of outer-kinetochore proteins from CENP-A chromatin.

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Figure 1: The kinetochore components CeCENP-A, CeCENP-C and KNL-1 are recruited to meiotic chromosomes during late pachytene/diplotene.
Figure 2: The targeting of CeCENP-C and KNL-1 to chromosomes during meiotic prophase requires CeCENP-A.
Figure 3: Conserved chromatin-proximal and outer-kinetochore components exhibit distinct localization patterns during meiosis.
Figure 4: Outer-kinetochore proteins still localize to the chromosome surface during meiosis in CeCENP-A-depleted embryos.
Figure 5: Embryos depleted of CeCENP-A or CeCENP-C exhibit normal meiotic segregation followed by a severe mitotic segregation defect.

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Acknowledgements

We thank J. McGhee for strain JM93 and members of the Oegema and Desai laboratories for support and discussions. J.M. is supported by the University of California, San Diego Genetics Training Grant; P.S.M. is the Fayez Sarofim Fellow of the Damon Runyon Cancer Research; K.O. is a Pew Scholar in the Biomedical Sciences; A.D. is the Connie and Bob Lurie Scholar of the Damon Runyon Cancer Research Foundation. This work was supported, in part, by a grant from the National Institutes of Health to A.D. (R01GM074215-01); A.D. and K.O. also receive salary and additional support from the Ludwig Institute for Cancer Research. A.D. and K.O. made the preliminary observations that led to this study. P.S.M. helped to generate and characterize the GFP–CPAR-1 strain. F.H. analysed the relative expression of CENP-A-like proteins. J.M. performed all of the other experiments, and J.M., K.O. and A.D. jointly prepared the manuscript.

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  1. Department of Cellular and Molecular Medicine, Ludwig Institute for Cancer Research, UCSD Biomedical Sciences Graduate Program, UCSD CMM-E, Room 3052, 9500 Gilman Drive, La Jolla, 92093-0653, CA, USA

    Joost Monen, Paul S. Maddox, Francie Hyndman, Karen Oegema, Karen Oegema & Arshad Desai

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Monen, J., Maddox, P., Hyndman, F. et al. Differential role of CENP-A in the segregation of holocentric C. elegans chromosomes during meiosis and mitosis. Nat Cell Biol 7, 1248–1255 (2005). https://doi.org/10.1038/ncb1331

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