Diaphanous formin mDia2 regulates CENP-A levels at centromeres

Liu, Chenshu; Mao, Yinghui

doi:10.1083/jcb.201512034

Cited by 22 publications

(35 citation statements)

References 37 publications

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“…22 Such a constitutively active construct of mDia2 is able to rescue the CENP-A loading defect resulted from depletion of MgcRacGAP. 30 This epistatic analysis suggests that mDia2 is the effector downstream of the MgcRacGAP-mediated small GTPase switch in maintaining CENP-A levels at centromeres.…”

Section: A Rho Family Small Gtpase Molecular Switch Is Required For Nmentioning

confidence: 99%

“…Knocking down mDia2 does not affect HJURP recruitment onto the centromere. 30 However, upon mDia2 depletion, the percentage of cells with their centromeres decorated with HJURP is substantially increased. 30 A reasonable explanation for a prolonged centromeric localization of HJURP is that the transient HJURP turnover at early G1 centromeres is delayed in the absence of mDia2.…”

Section: A New Model Of Epigenetic Regulation Of Centromeric Nucleosomentioning

confidence: 99%

“…38 Consistent with the hypothesis that the actin nucleation activity of mDia2 is important for new CENP-A loading, constitutively active mDia2 constructs with point mutations that have been shown to be defective in polymerizing actin filaments in vitro and in vivo, 17 unlike the wild-type constitutively active construct, are not able to rescue centromeric CENP-A levels upon depleting endogenous mDia2. 30 …”

Section: A Rho Family Small Gtpase Molecular Switch Is Required For Nmentioning

confidence: 99%

“…2) along with pulse chase approaches demonstrate that cells depleted of mDia2 are unable to maintain the continuous loading of new CENP-A onto centromeres. 30 The formin mDia2 have been shown to be the effector of either Rac or Cdc42, 20,21,23 2 small GTPases whose depletion results in a similar centromeric CENP-A reduction phenotype. 15 Unlike mDia1 or mDia3, mDia2 shuttles from cytoplasm to nucleoplasm evidenced by nuclear accumulation upon LMB treatment 31 and a clear nuclear distribution in early G1 cells (Fig.…”

Section: A Rho Family Small Gtpase Molecular Switch Is Required For Nmentioning

confidence: 99%

“…While investigating kinetochore functions of formin mDia3 28,29 using quantitative imaging, we have unexpectedly observed that depleting mDia2, but not mDia3, results in an almost 50% reduction of total CENP-A levels at centromeres after one round of cell cycle. 30 Furthermore, ratiometric live cell imaging studies (Fig. 2) along with pulse chase approaches demonstrate that cells depleted of mDia2 are unable to maintain the continuous loading of new CENP-A onto centromeres.…”

Section: A Rho Family Small Gtpase Molecular Switch Is Required For Nmentioning

confidence: 99%

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Formin-mediated epigenetic maintenance of centromere identity

Liu

Mao

2016

Small GTPases

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Accurate chromosome segregation in mammalian cells is guided by the centromere, a specialized chromosome region defined by the histone H3 variant centromere protein A (CENP-A). It is not well understood how cells maintain CENP-A levels at centromeres while continuously going through genome replications and cell divisions. A MgcRacGAP-dependent small GTPase molecular switch has been shown as essential for centromeric CENP-A maintenance. By using quantitative imaging, pulse-chase and live cell analysis, a recent work has suggested that the diaphanous formin mDia2, a well-established small GTPase effector, functions downstream of this small GTPase pathway to maintain CENP-A levels at centromeres. A constitutively active mDia2 construct is able to rescue the CENP-A loading defect caused by MgcRacGAP depletion. This study has uncovered an unsuspected role of the cytoskeleton protein mDia2 as an effector of the MgcRacGAP-dependent small GTPase signaling inside the nucleus to participate in the epigenetic regulation of centromere maintenance during cell cycle.

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Section: A Rho Family Small Gtpase Molecular Switch Is Required For Nmentioning

confidence: 99%

Section: A New Model Of Epigenetic Regulation Of Centromeric Nucleosomentioning

confidence: 99%

Section: A Rho Family Small Gtpase Molecular Switch Is Required For Nmentioning

confidence: 99%

Section: A Rho Family Small Gtpase Molecular Switch Is Required For Nmentioning

confidence: 99%

Section: A Rho Family Small Gtpase Molecular Switch Is Required For Nmentioning

confidence: 99%

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Formin-mediated epigenetic maintenance of centromere identity

Liu

Mao

2016

Small GTPases

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Quantitative Microscopy Reveals Centromeric Chromatin Stability, Size, and Cell Cycle Mechanisms to Maintain Centromere Homeostasis

Stanković

Jansen

2017

Centromeres and Kinetochores

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Centromeres are chromatin domains specified by nucleosomes containing the histone H3 variant, CENP-A. This unique centromeric structure is at the heart of a strong self-templating epigenetic mechanism that renders centromeres heritable. We review how specific quantitative microscopy approaches have contributed to the determination of the copy number, architecture, size, and dynamics of centromeric chromatin and its associated centromere complex and kinetochore. These efforts revealed that the key to long-term centromere maintenance is the slow turnover of CENP-A nucleosomes, a critical size of the chromatin domain and its cell cycle-coupled replication. These features come together to maintain homeostasis of a chromatin locus that directs its own epigenetic inheritance and facilitates the assembly of the mitotic kinetochore.

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Diverse functions for different forms of nuclear actin

Virtanen

Vartiainen

2017

Current Opinion in Cell Biology

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In addition to its essential roles as part of the cytoskeleton, actin has also been linked to many processes in the nucleus. Recent data has demonstrated the presence of both monomeric and polymeric actin in the nucleus, and implied distinct functional roles for these actin pools. Monomeric actin seems to be involved in regulation of gene expression through transcription factors, chromatin regulating complexes and RNA polymerases. In addition to cytoplasmic actin regulators, nuclear proteins, such as emerin, can regulate actin polymerization properties specifically in this compartment. Besides of structural roles, nuclear actin filaments may be required for organizing the nuclear contents and for the maintenance of genomic integrity.

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Diaphanous formin mDia2 regulates CENP-A levels at centromeres

Abstract: The diaphanous formin mDia2, a protein involved in cytoskeletal control, is required for new CENP-A loading at centromeres during the cell cycle to maintain epigenetic markers.

Cited by 22 publications

References 37 publications

Formin-mediated epigenetic maintenance of centromere identity

Formin-mediated epigenetic maintenance of centromere identity

Quantitative Microscopy Reveals Centromeric Chromatin Stability, Size, and Cell Cycle Mechanisms to Maintain Centromere Homeostasis

Diverse functions for different forms of nuclear actin

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