Molecular Strategies of Meiotic Cheating by Selfish Centromeres

Akera, Takashi; Trimm, Emily; Lampson, Michael A.

doi:10.1016/j.cell.2019.07.001

Cited by 95 publications

(125 citation statements)

References 72 publications

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“…In any case, CENP-A has a similar centromere enrichment profile to that of CENP-B (Fig EV5F and G), in accordance to the fact that CENP-A binding is proportional to centromere length [it tends to occupy~25-30% of the higher order repeats array (Sullivan et al, 2011); Table EV2]. Other (peri-)centromeric features could impact on chromosome-specific aneuploidy in a kinetochore-independent manner, among which we can mention variations within HOR arrays such as SNPs and indels (Sullivan et al, 2017), changes in the heterochromatin surrounding functional centromeres (Pezer & Ugarkovi c, 2008), fluctuations in centromere transcripts (Smurova & De Wulf, 2018), DNA methylation (Scelfo & Fachinetti, 2019), and variation in centromeric cohesion (Kitajima et al, 2006) and/or in microtubule-destabilizing activity (Akera et al, 2019). All these factors can potentially promote different patterns of chromosomespecific aneuploidy.…”

Section: Discussionmentioning

confidence: 99%

Human chromosome‐specific aneuploidy is influenced by DNA ‐dependent centromeric features

et al. 2019

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Intrinsic genomic features of individual chromosomes can contribute to chromosome-specific aneuploidy. Centromeres are key elements for the maintenance of chromosome segregation fidelity via a specialized chromatin marked by CENP-A wrapped by repetitive DNA. These long stretches of repetitive DNA vary in length among human chromosomes. Using CENP-A genetic inactivation in human cells, we directly interrogate if differences in the centromere length reflect the heterogeneity of centromeric DNA-dependent features and whether this, in turn, affects the genesis of chromosome-specific aneuploidy. Using three distinct approaches, we show that mis-segregation rates vary among different chromosomes under conditions that compromise centromere function. Whole-genome sequencing and centromere mapping combined with cytogenetic analysis, small molecule inhibitors, and genetic manipulation revealed that inter-chromosomal heterogeneity of centromeric features, but not centromere length, influences chromosome segregation fidelity. We conclude that faithful chromosome segregation for most of human chromosomes is biased in favor of centromeres with high abundance of DNA-dependent centromeric components. These inter-chromosomal differences in centromere features can translate into non-random aneuploidy, a hallmark of cancer and genetic diseases.

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Section: Discussionmentioning

confidence: 99%

Human chromosome‐specific aneuploidy is influenced by DNA ‐dependent centromeric features

et al. 2019

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“…Cells were suspended in 100 mM sucrose and were then spread on a thin layer of paraformaldehyde solution containing Triton X-100. The following primary antibodies were used for immunofluorescence analyses: rabbit anti-SYCP1 (1:100, catalog number ab15090, Abcam), mouse anti-SYCP1 (1:200; a gift from C. Hoog), guinea pig anti-SYCP2 (43), mouse anti-SYCP3 (1:200; catalog number ab97672, Abcam), rabbit anti-SYCP3 (1:200; 23024-1-AP), rabbit anti-SKP1 (1:50; catalog number ab10546, Abcam), rabbit anti-HORMAD1 (12), rabbit anti-HORMAD1 (1:200; 13917-1-AP, Proteintech Group), rabbit anti-HORMAD2 (10), mouse anti-H2AX (1:500; catalog number 16-202A, clone JBW301, Millipore), guinea pig anti-H1T (1:500; a gift from M. A. Handel) (4), rabbit anti-RPA2 (1:200; UP2436) (15), mouse anti-MLH1 (1:50; catalog number 550838, clone G168-15, BD Biosciences), human anti-CREST (1:100; 15-234, Antibodies Incorporated), mouse anti-CCNB1 (1:200; ab72, Abcam), rabbit anti-pHH3 (1:300; 9701S, Cell Signaling Technology), rabbit anti-PLK1 (1:50; UP2456; this study), mouse anti-BUB1 (1:50; a gift from Y. Watanabe) (44,45), and rabbit anti-CENP-C (1:500; a gift from Y. Watanabe) (46).…”

Section: Histological Immunofluorescence and Surface Nuclear Spreadmentioning

confidence: 99%

SKP1 drives the prophase I to metaphase I transition during male meiosis

Guan

Leu

et al. 2020

Sci. Adv.

Self Cite

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The meiotic prophase I to metaphase I (PI/MI) transition requires chromosome desynapsis and metaphase competence acquisition. However, control of these major meiotic events is poorly understood. Here, we identify an essential role for SKP1, a core subunit of the SKP1-Cullin-F-box (SCF) ubiquitin E3 ligase, in the PI/MI transition. SKP1 localizes to synapsed chromosome axes and evicts HORMAD proteins from these regions in meiotic spermatocytes. SKP1-deficient spermatocytes display premature desynapsis, precocious pachytene exit, loss of PLK1 and BUB1 at centromeres, but persistence of HORMAD, H2AX, RPA2, and MLH1 in diplonema. Strikingly, SKP1-deficient spermatocytes show sharply reduced MPF activity and fail to enter MI despite treatment with okadaic acid. SKP1deficient oocytes exhibit desynapsis, chromosome misalignment, and progressive postnatal loss. Therefore, SKP1 maintains synapsis in meiosis of both sexes. Furthermore, our results support a model where SKP1 functions as the long-sought intrinsic metaphase competence factor to orchestrate MI entry during male meiosis. , SKP1 drives the prophase I to metaphase I transition during male meiosis.

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“…Together, these findings suggest that the inbreeding process itself might drive the homogenization of satellite arrays and facilitates the fixation of larger centromeres. Indeed, prior studies have established that larger centromeres may recruit more kinetochore proteins than smaller centromeres, enabling larger centromeres to selfishly bias their own segregation into the oocyte during asymmetric female meiosis, a process known as centromere drive (Akera, Trimm, & Lampson, 2019; Chmátal et al, 2014; Iwata-Otsubo et al, 2017). In the context of inbreeding, such “strong centromeres” should be rapidly fixed.…”

Section: Discussionmentioning

confidence: 99%

Population and species diversity at mouse centromere satellites

Arora

Charlebois

Lawal

et al. 2020

Preprint

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Centromeres are satellite-rich chromatin domains that are essential for chromosome segregation. Centromere satellites evolve rapidly between species but little is known about population-level diversity across these loci. We developed a k-mer based method to quantify centromere copy number and sequence variation from whole genome sequencing data. We applied this method to diverse inbred and wild house mouse (genus Mus) genomes and uncover pronounced variation in centromere architecture between strains and populations. We show that patterns of centromere diversity do not mirror the known ancestry of inbred strains, revealing a remarkably rapid rate of centromere sequence evolution. We document increased satellite homogeneity and copy number in inbred compared to wild mice, suggesting that inbreeding remodels mouse centromere architecture. Our results highlight the power of k-mer based approaches for probing variation across repetitive regions and provide the first in-depth, phylogenetic portrait of centromere variation across Mus musculus.

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Molecular Strategies of Meiotic Cheating by Selfish Centromeres

Cited by 95 publications

References 72 publications

Human chromosome‐specific aneuploidy is influenced by DNA ‐dependent centromeric features

Human chromosome‐specific aneuploidy is influenced by DNA ‐dependent centromeric features

SKP1 drives the prophase I to metaphase I transition during male meiosis

Population and species diversity at mouse centromere satellites

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