Fig. 5: Human acrocentric chromosomes frequently form erroneous kinetochore-microtubule attachments.

a Schematic representation of bivalents kinetochores with telomeres in proximity and with kinetochores without telomere in proximity. Chromosomes in blue; kinetochores in magenta; telomeres in cyan; chiasmata in white. b Representative examples of immunofluorescence Airyscan images of human bivalents with kinetochores with telomeres in proximity and kinetochores without telomeres in proximity. Bivalent chromosomes are expected to have 8 telomeres, but in some cases, subsets of telomeres are in close proximity of each other so that fewer than 8 spots are detected Magenta, kinetochores, (ACA); cyan, telomeres, (TRF-2); blue, chromosome, (pH3). Scale bar, 0.5 μm. Representative examples of chromosomes from 10 immunolabelled human oocytes. c Illustrations and representative immunofluorescence images of kinetochore-microtubule attachments from cold-treated human oocytes in meiosis I. Overview images of a z-plane of the spindle (top row) and insets of the attachments at the bottom rows. Insets are magnifications of regions marked by dashed line boxes in the overview image. Arrowheads indicate the specified attachment type. Magenta, kinetochores, (ACA); cyan, telomeres, (TRF-2); blue, chromosome, (pH3); green microtubules (a-tubulin). Scale bar, 1 μm for both overview and insets. d Quantification of the proportion of the different kinetochore-microtubule attachments in kinetochores with telomeres in proximity and kinetochores without telomere in proximity (10 oocytes analysed). Two-sided Fisher’s exact test (end-on, p = 0.0044; lateral/merotelic, p = 0.0235; unattached, p = 0.1268; N/A, p = 1.000). e Illustrations and representative immunofluorescence images with telomere-masked kinetochores (top row) and exposed kinetochores (bottom row) from human oocytes. Magenta, kinetochores, (ACA); cyan, telomeres, (TRF-2); blue, chromosomes, (Hoechst). Scale bar 0.5 μm. f Proportion of telomere-masked and exposed kinetochores in acrocentric chromosomes from the total kinetochores of acrocentric chromosomes examined (10 oocytes analysed). g Quantification of the proportion of the different kinetochore-microtubule (Kt-Mt) attachment types for telomere-masked and exposed kinetochores of acrocentric chromosomes in human oocytes (10 oocytes analysed). Two-sided Fisher’s exact test (end-on, p = 0.0017; unattached, p = 0.0160). Number of chromosomes or kinetochores analysed is indicated in brackets under each category. P-values in the graphs are indicated as follows, *p < 0.05, **p < 0.01, ***p < 0.001, and n.s.: non-significant. The number of cells is indicated in brackets in the figure legend.