Molecular basis of MKLP2-dependent Aurora B transport from chromatin to the anaphase central spindle

Serena, Michela; Bastos, Ricardo; Elliott, P.R.; Barr, Francis A.

doi:10.1083/jcb.201910059

Cited by 34 publications

(32 citation statements)

References 62 publications

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“…Inhibition of Chk2 impairs CPC or Mklp2 localization inside the FB in late midbodies; furthermore, expression of nonphosphorylatable INCENP-Ser91A that does not efficiently bind to Mklp2 impairs INCENP or Mklp2 localization to the midbody arms and the midbody center in early or late midbodies. These results are consistent with previous reports that CPC and Mklp2 mutually depend on each other for midzone/midbody localization by Mklp2 transporting CPC along central spindle microtubules and CPC binding promoting the microtubule processivity of Mklp2 in cytokinesis ( Adriaans et al, 2020 ; Hümmer and Mayer, 2009 ; Kitagawa et al, 2013 ; Serena et al, 2020 ). Of note, however, INCENP binding to Mklp2 is not required for Mklp2’s interaction with the midbody protein Cep55 by GST pull-downs when proteins can freely interact in cell extracts, indicating the CPC–Mklp2 complex localizes to the midbody center through Mklp2 binding to Cep55.…”

Section: Discussionsupporting

confidence: 93%

An ATM–Chk2–INCENP pathway activates the abscission checkpoint

Petsalaki

Zachos

2020

Journal of Cell Biology

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During cell division, in response to chromatin bridges, the chromosomal passenger complex (CPC) delays abscission to prevent chromosome breakage or tetraploidization. Here, we show that inhibition of ATM or Chk2 kinases impairs CPC localization to the midbody center, accelerates midbody resolution in normally segregating cells, and correlates with premature abscission and chromatin breakage in cytokinesis with trapped chromatin. In cultured human cells, ATM activates Chk2 at late midbodies. In turn, Chk2 phosphorylates human INCENP-Ser91 to promote INCENP binding to Mklp2 kinesin and CPC localization to the midbody center through Mklp2 association with Cep55. Expression of truncated Mklp2 that does not bind to Cep55 or nonphosphorylatable INCENP-Ser91A impairs CPC midbody localization and accelerates abscission. In contrast, expression of phosphomimetic INCENP-Ser91D or a chimeric INCENP protein that is targeted to the midbody center rescues the abscission delay in Chk2-deficient or ATM-deficient cells. Furthermore, the Mre11–Rad50–Nbs1 complex is required for ATM activation at the midbody in cytokinesis with chromatin bridges. These results identify an ATM–Chk2–INCENP pathway that imposes the abscission checkpoint by regulating CPC midbody localization.

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Section: Discussionsupporting

confidence: 93%

An ATM–Chk2–INCENP pathway activates the abscission checkpoint

Petsalaki

Zachos

2020

Journal of Cell Biology

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“…This suggests that another CPC recruitment factor is lacking or reduced at the neocentromere. Possibly, the CPC requires specific chromatin features, which may include DNA sequences features present within α-satellite DNA as recently suggested ( Serena et al, 2020 ) or the structure of pericentric heterochromatin. In fact, HP1 is involved in CPC recruitment ( Ruppert et al, 2018 ), and decreasing centromeric heterochromatin reduces CPC levels ( Molina et al, 2016b ).…”

Section: Resultsmentioning

confidence: 91%

“…S3 A ). The gradual increase of INCENP is of interest, as INCENP directly contacts chromatin ( Jeyaprakash et al, 2007 ; Klein et al, 2006 ; Serena et al, 2020 ). It is possible that chromatin structure is changing through successive divisions driving more INCENP to accumulate.…”

Section: Resultsmentioning

confidence: 99%

Induction of spontaneous human neocentromere formation and long-term maturation

Murillo-Pineda

Valente

Dumont

et al. 2021

Journal of Cell Biology

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Human centromeres form primarily on α-satellite DNA but sporadically arise de novo at naive ectopic loci, creating neocentromeres. Centromere inheritance is driven primarily by chromatin containing the histone H3 variant CENP-A. Here, we report a chromosome engineering system for neocentromere formation in human cells and characterize the first experimentally induced human neocentromere at a naive locus. The spontaneously formed neocentromere spans a gene-poor 100-kb domain enriched in histone H3 lysine 9 trimethylated (H3K9me3). Long-read sequencing revealed this neocentromere was formed by purely epigenetic means and assembly of a functional kinetochore correlated with CENP-A seeding, eviction of H3K9me3 and local accumulation of mitotic cohesin and RNA polymerase II. At formation, the young neocentromere showed markedly reduced chromosomal passenger complex (CPC) occupancy and poor sister chromatin cohesion. However, long-term tracking revealed increased CPC assembly and low-level transcription providing evidence for centromere maturation over time.

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“…Survivin is associated with the kinetochores and is translocated to the spindle midzone during anaphase in HeLa cells [14]. Recent studies set up a link and indicate that KIF20A/MKLP2 localize the chromosomal passenger complex (CPC) with the members Aurora B, INCENP, survivin and borealin to the spindle midzone as a kinesin-like motor protein for cytokinesis [15][16][17][18], while Cdk1 could coordinate the activation of MKLP2 with CPC for cytokinesis [19,20].…”

Section: Introductionmentioning

confidence: 99%

PRC1 is a critical regulator for anaphase spindle midzone assembly and cytokinesis in mouse oocyte meiosis

Pan

et al. 2020

The FEBS Journal

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Protein regulator of cytokinesis 1 (PRC1) is a microtubule bundling protein that is involved in the regulation of the central spindle bundle and spindle orientation during mitosis. However, the functions of PRC1 during meiosis have rarely been studied. In this study, we explored the roles of PRC1 during meiosis using an oocyte model. Our results found that PRC1 was expressed at all stages of mouse oocyte meiosis, and PRC1 accumulated in the midzone/midbody during anaphase/telophase I. Moreover, depleting PRC1 caused defects in polar body extrusion during mouse oocyte maturation. Further analysis found that PRC1 knockdown did not affect meiotic spindle formation or chromosome segregation; however, deleting PRC1 prevented formation of the midzone and midbody at the anaphase/telophase stage of meiosis I, which caused cytokinesis defects and further induced the formation of two spindles in the oocytes. PRC1 knockdown increased the level of tubulin acetylation, indicating that microtubule stability was affected. Furthermore, KIF4A and PRC1 showed similar localization in the midzone/midbody of oocytes at anaphase/telophase I, while the depletion of KIF4A affected the expression and localization of PRC1. The PRC1 mRNA injection rescued the defects caused by PRC1 knockdown in oocytes. In summary, our results suggest that PRC1 is critical for midzone/midbody formation and cytokinesis under regulation of KIF4A in mouse oocytes.

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Molecular basis of MKLP2-dependent Aurora B transport from chromatin to the anaphase central spindle

Cited by 34 publications

References 62 publications

An ATM–Chk2–INCENP pathway activates the abscission checkpoint

An ATM–Chk2–INCENP pathway activates the abscission checkpoint

Induction of spontaneous human neocentromere formation and long-term maturation

PRC1 is a critical regulator for anaphase spindle midzone assembly and cytokinesis in mouse oocyte meiosis

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