A Centromere-Signaling Network Underlies the Coordination among Mitotic Events

Trivedi, Prasad; Stukenberg, P. Todd

doi:10.1016/j.tibs.2015.11.002

Cited by 54 publications

(50 citation statements)

References 118 publications

(185 reference statements)

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“…We therefore conclude that Haspin ensures mitotic chromosome biorientation not only by promoting the H3pT3-dependent centromeric localization of CPC to correct improper KT-MT attachments, but also by antagonizing Wapl to protect centromeric cohesin ( Fig 5J). This study provides new insight into how different factors in the complex centromere signaling network are specialized to meet the multiple challenges encountered on the road to accurate chromosome segregation in mitosis [70].…”

Section: Resultsmentioning

confidence: 99%

A kinase‐dependent role for Haspin in antagonizing Wapl and protecting mitotic centromere cohesion

Cai

Chen

et al. 2017

EMBO Reports

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Sister-chromatid cohesion mediated by the cohesin complex is fundamental for precise chromosome segregation in mitosis. Through binding the cohesin subunit Pds5, Wapl releases the bulk of cohesin from chromosome arms in prophase, whereas centromeric cohesin is protected from Wapl until anaphase onset. Strong centromere cohesion requires centromeric localization of the mitotic histone kinase Haspin, which is dependent on the interaction of its non-catalytic N-terminus with Pds5B. It remains unclear how Haspin fully blocks the Wapl-Pds5B interaction at centromeres. Here, we show that the C-terminal kinase domain of Haspin (Haspin-KD) binds and phosphorylates the YSR motif of Wapl (Wapl-YSR), thereby directly inhibiting the YSR motif-dependent interaction of Wapl with Pds5B. Cells expressing a Wapl-binding-deficient mutant of Haspin or treated with Haspin inhibitors show centromeric cohesion defects. Phospho-mimetic mutation in Wapl-YSR prevents Wapl from binding Pds5B and releasing cohesin. Forced targeting Haspin-KD to centromeres partly bypasses the need for Haspin-Pds5B interaction in cohesion protection. Taken together, these results indicate a kinase-dependent role for Haspin in antagonizing Wapl and protecting centromeric cohesion in mitosis.

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Section: Resultsmentioning

confidence: 99%

A kinase‐dependent role for Haspin in antagonizing Wapl and protecting mitotic centromere cohesion

Cai

Chen

et al. 2017

EMBO Reports

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“…Many of the motors and associated proteins are controlled by kinases that alter binding through specific phosphorylation sites Together, this regulation constitutes the spindle checkpoint – a feedback system used to ensure correct chromosome separation during mitosis. 71 We discuss these biological examples of microtubule network organization under feedback control and producing work in live cells below.…”

Section: Feedback and Control In The Assembly Of Tubulin Into Microtumentioning

confidence: 99%

“…137 The underlying structure of the mitotic spindle is not that complex, but the non-equilibrium maintenance, information processing, feedback control, and resulting work that results in the splitting of the genetic material into two new cells is still being elucidated. A recent review by Trivedi and Stukenberg postulate a double feedback loop control system to control the mechanical and chemical signaling in the kinetochore/centromere “checkpoint” system that could control when the spindle decides to divide, 71 so we will not go through it completely here. Instead, we will highlight a few examples involving microtubules and motors relevant to the active, non-equilibrium systems described above.…”

Section: Complex Controlled Non-equilibrium Feedback In Biologymentioning

confidence: 99%

Non-equilibrium assembly of microtubules: from molecules to autonomous chemical robots

2017

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Biological systems have evolved to harness non-equilibrium processes from the molecular to the macro scale. It is currently a grand challenge of chemistry, materials science, and engineering to understand and mimic biological systems that have the ability to autonomously sense stimuli, process these inputs, and respond by performing mechanical work. New chemical systems are responding to the challenge and form the basis for future responsive, adaptive, and active materials. In this article, we describe a particular biochemical-biomechanical network based on the microtubule cytoskeletal filament – itself a non-equilibrium chemical system. We trace the non-equilibrium aspects of the system from molecules to networks and describe how the cell uses this system to perform active work in essential processes. Finally, we discuss how microtubule-based engineered systems can serve as testbeds for autonomous chemical robots composed of biological and synthetic components.

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“…Aurora B kinase activity is required for spindle assembly in Drosophila oocytes [31] and can be antagonized by PP1 in other systems [32]. Furthermore, they have opposite phenotypes: both karyosome and sister centromeres preciously separate in Pp1-87B RNAi oocytes but remain together in Aurora B-depleted oocytes [31].…”

Section: Separase-independent Loss Of Sister Centromere Fusion Dependmentioning

confidence: 99%

Cohesin and microtubule dependent mechanisms regulate sister centromere fusion during meiosis I

McKim

Wang

Das

2019

Preprint

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Sister centromere fusion is a process unique to meiosis that promotes co-orientation of the sister kinetochores, ensuring they attach to microtubules from the same pole. We have found that the kinetochore protein SPC105R/KNL1 and Protein Phosphatase 1 (PP1-87B) are required for this process. The analysis of these two proteins, however, has shown that two independent mechanisms maintain sister centromere fusion during meiosis I in Drosophila oocytes. Double depletion experiments demonstrated that the precocious separation of centromeres in Spc105RRNAi oocytes is Separase-dependent, suggesting cohesin proteins must be maintained at the core centromeres. In contrast, precocious sister centromere separation in Pp1-87B RNAi oocytes does not depend on Separase or Wapl. Further analysis with microtubule destabilizing drugs showed that PP1-87B maintains sister centromeres fusion by regulating microtubule dynamics.Additional double depletion experiments demonstrated that PP1-87B has this function by antagonizing Polo kinase and BubR1, two proteins known to promote kinetochore-microtubule (KT-MT) attachments. These results suggest that PP1-87B maintains sister centromere fusion by inhibiting stable KT-MT attachments. Surprisingly, we found that loss of C(3)G, the transverse element of the synaptonemal complex (SC), suppresses centromere separation in Pp1-87B RNAi oocytes. This is evidence for a functional role of centromeric SC in the meiotic divisions. We propose two mechanisms maintain co-orientation in Drosophila oocytes: one involves SPC105R to protect cohesins at sister centromeres and another involves PP1-87B to regulate spindle forces at end-on attachments. Author SummaryMeiosis involves two cell divisions. In the first division, pairs of homologous chromosomes segregate, in the second division, the sister chromatids segregate. These patterns of division are mediated by regulating microtubule attachments to the kinetochores and stepwise release of cohesion between the sister chromatids. During meiosis I, cohesion fusing sister centromeres must be intact so they attach to microtubules from the same pole. At the same time, arm cohesion must be released for anaphase I. Upon entry into meiosis II, the sister centromeres must separate to allow attachment to opposite poles, while cohesion surrounding the centromeres must remain intact until anaphase II. How these different populations of cohesion are regulated is not understood. We identified two genes required for maintaining sister centromere cohesion, and surprisingly found they define two distinct mechanisms. The first is a kinetochore protein that maintains sister centromere fusion by recruiting proteins that protect cohesion. The second is a phosphatase that antagonizes proteins that stabilize microtubule attachments. We propose that entry into meiosis II coincides with stabilization of microtubule attachments, resulting in the separation of sister centromeres without disrupting cohesion in other regions, facilitating attachment of sister chromatids to opposite poles.

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A Centromere-Signaling Network Underlies the Coordination among Mitotic Events

Cited by 54 publications

References 118 publications

A kinase‐dependent role for Haspin in antagonizing Wapl and protecting mitotic centromere cohesion

A kinase‐dependent role for Haspin in antagonizing Wapl and protecting mitotic centromere cohesion

Non-equilibrium assembly of microtubules: from molecules to autonomous chemical robots

Cohesin and microtubule dependent mechanisms regulate sister centromere fusion during meiosis I

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