HJURP is a CENP-A chromatin assembly factor sufficient to form a functional de novo kinetochore

Abstract Centromeres of higher eukaryotes are epigenetically marked by the centromere-specific CENP-A nucleosome. New CENP-A recruitment requires the CENP-A histone chaperone HJURP. In this paper, we show that a LacI (Lac repressor) fusion of HJURP drove the stable recruitment of CENP-A to a LacO (Lac operon) array at a noncentromeric locus. Ectopically targeted CENP-A chromatin at the LacO array was … Continue reading

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APC/CCdh1-dependent proteolysis of USP1 regulates the response to UV-mediated DNA damage

Cotto-Rios et al. Abstract Targeted protein destruction of critical cellular regulators during the G1 phase of the cell cycle is achieved by anaphase-promoting complex/cyclosomeCdh1 (APC/CCdh1), a multisubunit E3 ubiquitin ligase. Cells lacking Cdh1 have been shown to accumulate deoxyribonucleic acid (DNA) damage, suggesting that it may play a previously unrecognized role in maintaining genomic stability. The ubiquitin-specific protease 1 (USP1) … Continue reading

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Repeated cleavage failure does not establish centrosome amplification in untransformed human cells

Krzywicka-Racka and Sluder 194 (2): 199 Abstract We tested whether cleavage failure as a transient event establishes an incidence of centrosome amplification in cell populations. Five rounds of ∼30% cytochalasin-induced cleavage failure in untransformed human cell cultures did not establish centrosome amplification in the short or long terms. The progeny of binucleate cells progressively dropped out of the cell cycle … Continue reading

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Nuclear translocation of AMPK-α1 potentiates striatal neurodegeneration in Huntington’s disease

Abstract Adenosine monophosphate–activated protein kinase (AMPK) is a major energy sensor that maintains cellular energy homeostasis. Huntington’s disease (HD) is a neurodegenerative disorder caused by the expansion of CAG repeats in the huntingtin (Htt) gene. In this paper, we report that activation of the α1 isoform of AMPK (AMPK-α1) occurred in striatal neurons of humans and mice with HD. Overactivation … Continue reading

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Transient binding of an activator BH3 domain to the Bak BH3-binding groove initiates Bak oligomerization

Abstract The mechanism by which the proapoptotic Bcl-2 family members Bax and Bak release cytochrome c from mitochondria is incompletely understood. In this paper, we show that activator BH3-only proteins bind tightly but transiently to the Bak hydrophobic BH3-binding groove to induce Bak oligomerization, liposome permeabilization, mitochondrial cytochrome c release, and cell death. Analysis by surface plasmon resonance indicated that … Continue reading

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α-Synuclein and ALPS motifs are membrane curvature sensors whose contrasting chemistry mediates selective vesicle binding

Pranke et al. 194 (1): 89 Abstract Membrane curvature sensors have diverse structures and chemistries, suggesting that they might have the intrinsic capacity to discriminate between different types of vesicles in cells. In this paper, we compare the in vitro and in vivo membrane-binding properties of two curvature sensors that form very different amphipathic helices: the amphipathic lipid-packing sensor (ALPS) … Continue reading

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POM121 and Sun1 play a role in early steps of interphase NPC assembly

Talamas and Hetzer 194 (1): 27 Abstract Nuclear pore complexes (NPCs) assemble at the end of mitosis during nuclear envelope (NE) reformation and into an intact NE as cells progress through interphase. Although recent studies have shown that NPC formation occurs by two different molecular mechanisms at two distinct cell cycle stages, little is known about the molecular players that … Continue reading

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HJURP puts the centromere in place

HJURP puts the centromere in place The histone chaperone HJURP directs the formation of functional centromeres by assembling the histone variant CENP-A into chromatin, Barnhart et al. reveal. CENP-A is a specialized version of histone H3 that marks the position of centromeres. A protein called HJURP helps deliver CENP-A to centromeric chromatin, but whether HJURP simply protects CENP-A until the … Continue reading

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HJURP is a CENP-A chromatin assembly factor sufficient to form a functional de novo kinetochore

Barnhart et al. Abstract Centromeres of higher eukaryotes are epigenetically marked by the centromere-specific CENP-A nucleosome. New CENP-A recruitment requires the CENP-A histone chaperone HJURP. In this paper, we show that a LacI (Lac repressor) fusion of HJURP drove the stable recruitment of CENP-A to a LacO (Lac operon) array at a noncentromeric locus. Ectopically targeted CENP-A chromatin at the … Continue reading

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α-Synuclein and ALPS motifs are membrane curvature sensors whose contrasting chemistry mediates selective vesicle binding

Pranke et al. 194 (1): 89 Abstract Membrane curvature sensors have diverse structures and chemistries, suggesting that they might have the intrinsic capacity to discriminate between different types of vesicles in cells. In this paper, we compare the in vitro and in vivo membrane-binding properties of two curvature sensors that form very different amphipathic helices: the amphipathic lipid-packing sensor (ALPS) … Continue reading

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