Roles of replication fork-interacting and Chk1-activating domains from Claspin in a DNA replication checkpoint response.

Abstract:

:Claspin is essential for the ATR-dependent activation of Chk1 in Xenopus egg extracts containing incompletely replicated DNA. Claspin associates with replication forks upon origin unwinding. We show that Claspin contains a replication fork-interacting domain (RFID, residues 265-605) that associates with Cdc45, DNA polymerase epsilon, replication protein A, and two replication factor C complexes on chromatin. The RFID contains two basic patches (BP1 and BP2) at amino acids 265-331 and 470-600, respectively. Deletion of either BP1 or BP2 compromises optimal binding of Claspin to chromatin. Absence of BP1 has no effect on the ability of Claspin to mediate activation of Chk1. By contrast, removal of BP2 causes a large reduction in the Chk1-activating potency of Claspin. We also find that Claspin contains a small Chk1-activating domain (residues 776-905) that does not bind stably to chromatin, but it is fully effective at high concentrations for mediating activation of Chk1. These results indicate that stable retention of Claspin on chromatin is not necessary for activation of Chk1. Instead, our findings suggest that only transient interaction of Claspin with replication forks potentiates its Chk1-activating function. Another implication of this work is that stable binding of Claspin to chromatin may play a role in other functions besides the activation of Chk1.

journal_name

Mol Biol Cell

authors

Lee J,Gold DA,Shevchenko A,Shevchenko A,Dunphy WG

doi

10.1091/mbc.e05-07-0671

keywords:

subject

Has Abstract

pub_date

2005-11-01 00:00:00

pages

5269-82

issue

11

eissn

1059-1524

issn

1939-4586

pii

E05-07-0671

journal_volume

16

pub_type

杂志文章
  • TGF beta-induced growth inhibition in primary fibroblasts requires the retinoblastoma protein.

    abstract::Transforming growth factor beta (TGF beta) inhibits cell proliferation by inducing a G1 cell-cycle arrest. Cyclin/CDK complexes have been implicated in this arrest, because TGF beta treatment leads to inhibition of cyclin/CDK activity. We have investigated the role of the retinoblastoma protein (pRb) in TGF beta-induc...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.7.9.1335

    authors: Herrera RE,Mäkelä TP,Weinberg RA

    更新日期:1996-09-01 00:00:00

  • Efficient interaction between two GTPases allows the chloroplast SRP pathway to bypass the requirement for an SRP RNA.

    abstract::Cotranslational protein targeting to membranes is regulated by two GTPases in the signal recognition particle (SRP) and the SRP receptor; association between the two GTPases is slow and is accelerated 400-fold by the SRP RNA. Intriguingly, the otherwise universally conserved SRP RNA is missing in a novel chloroplast S...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e07-01-0037

    authors: Jaru-Ampornpan P,Chandrasekar S,Shan SO

    更新日期:2007-07-01 00:00:00

  • Septins regulate junctional integrity of endothelial monolayers.

    abstract::Junctional integrity of endothelial monolayers is crucial to control movement of molecules and cells across the endothelium. Examining the structure and dynamics of cell junctions in endothelial monolayers, we discovered a role for septins. Contacts between adjacent endothelial cells were dynamic, with protrusions ext...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E18-02-0136

    authors: Kim J,Cooper JA

    更新日期:2018-07-15 00:00:00

  • Transforming growth factor beta enhances epithelial cell survival via Akt-dependent regulation of FKHRL1.

    abstract::The Forkhead family of transcription factors participates in the induction of death-related genes. In NMuMG and 4T1 mammary epithelial cells, transforming growth factor beta (TGF beta) induced phosphorylation and cytoplasmic retention of the Forkhead factor FKHRL1, while reducing FHKRL1-dependent transcriptional activ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.12.11.3328

    authors: Shin I,Bakin AV,Rodeck U,Brunet A,Arteaga CL

    更新日期:2001-11-01 00:00:00

  • A quantitative and semi-automated method for determining misaligned and lagging chromosomes during mitosis.

    abstract::Accurate chromosome alignment at metaphase facilitates the equal segregation of sister chromatids to each of the nascent daughter cells. Lack of proper metaphase alignment is an indicator of defective chromosome congression and aberrant kinetochore-microtubule attachments which in turn promotes chromosome missegregati...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E20-09-0585

    authors: Braga LG,Prifti DK,Garand C,Saini PK,Elowe S

    更新日期:2020-10-21 00:00:00

  • Two phosphatidylinositol 4-kinases control lysosomal delivery of the Gaucher disease enzyme, β-glucocerebrosidase.

    abstract::Gaucher disease is a lysosomal storage disorder caused by a defect in the degradation of glucosylceramide catalyzed by the lysosomal enzyme β-glucocerebrosidase (GBA). GBA reaches lysosomes via association with its receptor, lysosomal integral membrane protein type 2 (LIMP-2). We found that distinct phosphatidylinosit...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E11-06-0553

    authors: Jović M,Kean MJ,Szentpetery Z,Polevoy G,Gingras AC,Brill JA,Balla T

    更新日期:2012-04-01 00:00:00

  • Calreticulin couples calcium release and calcium influx in integrin-mediated calcium signaling.

    abstract::The engagement of integrin alpha7 in E63 skeletal muscle cells by laminin or anti-alpha7 antibodies triggered transient elevations in the intracellular free Ca(2+) concentration that resulted from both inositol triphosphate-evoked Ca(2+) release from intracellular stores and extracellular Ca(2+) influx through voltage...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.11.4.1433

    authors: Kwon MS,Park CS,Choi K,Ahnn J,Kim JI,Eom SH,Kaufman SJ,Song WK

    更新日期:2000-04-01 00:00:00

  • Phosphorylation by c-Jun NH2-terminal kinase 1 regulates the stability of transcription factor Sp1 during mitosis.

    abstract::The transcription factor Sp1 is ubiquitously expressed in different cells and thereby regulates the expression of genes involved in many cellular processes. This study reveals that Sp1 was phosphorylated during the mitotic stage in three epithelial tumor cell lines and one glioma cell line. By using different kinase i...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e07-09-0881

    authors: Chuang JY,Wang YT,Yeh SH,Liu YW,Chang WC,Hung JJ

    更新日期:2008-03-01 00:00:00

  • Characterization of Mayven, a novel actin-binding protein predominantly expressed in brain.

    abstract::The cytoskeleton plays an important role in neuronal morphogenesis. We have identified and characterized a novel actin-binding protein, termed Mayven, predominantly expressed in brain. Mayven contains a BTB (broad complex, tramtrack, bric-a-brac)/POZ (poxvirus, zinc finger) domain-like structure in the predicted N ter...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.10.7.2361

    authors: Soltysik-Espanola M,Rogers RA,Jiang S,Kim TA,Gaedigk R,White RA,Avraham H,Avraham S

    更新日期:1999-07-01 00:00:00

  • Protein kinase Czeta mediates insulin-induced glucose transport through actin remodeling in L6 muscle cells.

    abstract::Protein kinase C (PKC) zeta has been implicated in insulin-induced glucose uptake in skeletal muscle cell, although the underlying mechanism remains unknown. In this study, we investigated the effect of PKCzeta on actin remodeling and glucose transport in differentiated rat L6 muscle cells expressing myc-tagged glucos...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e05-10-0969

    authors: Liu LZ,Zhao HL,Zuo J,Ho SK,Chan JC,Meng Y,Fang FD,Tong PC

    更新日期:2006-05-01 00:00:00

  • Anchoring of protein kinase A-regulatory subunit IIalpha to subapically positioned centrosomes mediates apical bile canalicular lumen development in response to oncostatin M but not cAMP.

    abstract::Oncostatin M and cAMP signaling stimulate apical surface-directed membrane trafficking and apical lumen development in hepatocytes, both in a protein kinase A (PKA)-dependent manner. Here, we show that oncostatin M, but not cAMP, promotes the A-kinase anchoring protein (AKAP)-dependent anchoring of the PKA regulatory ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e06-08-0732

    authors: Wojtal KA,Hoekstra D,van Ijzendoorn SC

    更新日期:2007-07-01 00:00:00

  • Spatiotemporal dynamics of triglyceride storage in unilocular adipocytes.

    abstract::The spatiotemporal dynamics of triglyceride (TG) storage in unilocular adipocytes are not well understood. Here we applied ex vivo technology to study trafficking and metabolism of fluorescent fatty acids in adipose tissue explants. Live imaging revealed multiple cytoplasmic nodules surrounding the large central lipid...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E14-06-1085

    authors: Chu M,Sampath H,Cahana DY,Kahl CA,Somwar R,Cornea A,Roberts CT Jr,Varlamov O

    更新日期:2014-12-15 00:00:00

  • BAF-1 mobility is regulated by environmental stresses.

    abstract::Barrier to autointegration factor (BAF) is an essential component of the nuclear lamina that binds lamins, LEM-domain proteins, histones, and DNA. Under normal conditions, BAF protein is highly mobile when assayed by fluorescence recovery after photobleaching and fluorescence loss in photobleaching. We report that Cae...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E13-08-0477

    authors: Bar DZ,Davidovich M,Lamm AT,Zer H,Wilson KL,Gruenbaum Y

    更新日期:2014-04-01 00:00:00

  • Transcriptome analysis of tetraploid cells identifies cyclin D2 as a facilitator of adaptation to genome doubling in the presence of p53.

    abstract::Tetraploidization, or genome doubling, is a prominent event in tumorigenesis, primarily because cell division in polyploid cells is error-prone and produces aneuploid cells. This study investigates changes in gene expression evoked in acute and adapted tetraploid cells and their effect on cell-cycle progression. Acute...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E16-05-0268

    authors: Potapova TA,Seidel CW,Box AC,Rancati G,Li R

    更新日期:2016-10-15 00:00:00

  • Aneugenic activity of Op18/stathmin is potentiated by the somatic Q18-->e mutation in leukemic cells.

    abstract::Op18/stathmin (Op18) is a phosphorylation-regulated microtubule destabilizer that is frequently overexpressed in tumors. The importance of Op18 in malignancy was recently suggested by identification of a somatic Q18-->E mutation of Op18 in an adenocarcinoma. We addressed the functional consequences of aberrant Op18 ex...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e06-02-0165

    authors: Holmfeldt P,Brännström K,Stenmark S,Gullberg M

    更新日期:2006-07-01 00:00:00

  • Cytoplasmic and nuclear phospholipase C-beta 1 relocation: role in resumption of meiosis in the mouse oocyte.

    abstract::The location of the phospholipase C beta 1-isoform (PLC-beta 1) in the mouse oocyte and its role in the resumption of meiosis were examined. We used specific monoclonal antibodies to monitor the in vitro dynamics of the subcellular distribution of the enzyme from the release of the oocyte from the follicle until break...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.11.12.4369

    authors: Avazeri N,Courtot AM,Pesty A,Duquenne C,Lefèvre B

    更新日期:2000-12-01 00:00:00

  • Analysis of Na+,K+-ATPase motion and incorporation into the plasma membrane in response to G protein-coupled receptor signals in living cells.

    abstract::Dopamine (DA) increases Na(+),K(+)-ATPase activity in lung alveolar epithelial cells. This effect is associated with an increase in Na(+),K(+)-ATPase molecules within the plasma membrane (). Analysis of Na(+),K(+)-ATPase motion was performed in real-time in alveolar cells stably expressing Na(+),K(+)-ATPase molecules ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e02-06-0367

    authors: Bertorello AM,Komarova Y,Smith K,Leibiger IB,Efendiev R,Pedemonte CH,Borisy G,Sznajder JI

    更新日期:2003-03-01 00:00:00

  • ACT-5 is an essential Caenorhabditis elegans actin required for intestinal microvilli formation.

    abstract::Investigation of Caenorhabditis elegans act-5 gene function revealed that intestinal microvillus formation requires a specific actin isoform. ACT-5 is the most diverged of the five C. elegans actins, sharing only 93% identity with the other four. Green fluorescent protein reporter and immunofluorescence analysis indic...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e04-12-1061

    authors: MacQueen AJ,Baggett JJ,Perumov N,Bauer RA,Januszewski T,Schriefer L,Waddle JA

    更新日期:2005-07-01 00:00:00

  • Control of the mitotic exit network during meiosis.

    abstract::The mitotic exit network (MEN) is an essential GTPase signaling pathway that triggers exit from mitosis in budding yeast. We show here that during meiosis, the MEN is dispensable for exit from meiosis I but contributes to the timely exit from meiosis II. Consistent with a role for the MEN during meiosis II, we find th...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E12-03-0235

    authors: Attner MA,Amon A

    更新日期:2012-08-01 00:00:00

  • The thrill of scientific discovery and leadership with my group.

    abstract::My group and I feel tremendously honored to be recognized with the 2016 Early Career Life Scientist Award from the American Society for Cell Biology. In this essay I share the scientific questions that my lab has been excitedly pursuing since starting in August 2009 and the leadership behaviors we have adopted that en...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E16-06-0373

    authors: Greco V

    更新日期:2016-11-01 00:00:00

  • Protein targeting of an unusual, evolutionarily conserved adenylate kinase to a eukaryotic flagellum.

    abstract::The eukaryotic flagellum is a large structure into which specific constituent proteins must be targeted, transported and assembled after their synthesis in the cytoplasm. Using Trypanosoma brucei and a proteomic approach, we have identified and characterized a novel set of adenylate kinase proteins that are localized ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e04-03-0217

    authors: Pullen TJ,Ginger ML,Gaskell SJ,Gull K

    更新日期:2004-07-01 00:00:00

  • The two SAS-6 homologs in Tetrahymena thermophila have distinct functions in basal body assembly.

    abstract::Cilia and flagella are structurally and functionally conserved organelles present in basal as well as higher eukaryotes. The assembly of cilia requires a microtubule based scaffold called a basal body. The ninefold symmetry characteristic of basal bodies and the structurally similar centriole is organized around a hub...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e08-08-0838

    authors: Culver BP,Meehl JB,Giddings TH Jr,Winey M

    更新日期:2009-03-01 00:00:00

  • Protein folding state-dependent sorting at the Golgi apparatus.

    abstract::In eukaryotic cells, organelle-specific protein quality control (PQC) is critical for maintaining cellular homeostasis. Despite the Golgi apparatus being the major protein processing and sorting site within the secretory pathway, how it contributes to PQC has remained largely unknown. Using different chemical biology-...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E19-01-0069

    authors: Hellerschmied D,Serebrenik YV,Shao L,Burslem GM,Crews CM

    更新日期:2019-08-01 00:00:00

  • Actomyosin sliding is attenuated in contractile biomimetic cortices.

    abstract::Myosin II motors embedded within the actin cortex generate contractile forces to modulate cell shape in essential behaviors, including polarization, migration, and division. In sarcomeres, myosin II-mediated sliding of antiparallel F-actin is tightly coupled to myofibril contraction. By contrast, cortical F-actin is h...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E13-08-0450

    authors: Murrell M,Gardel ML

    更新日期:2014-06-15 00:00:00

  • A mechanism of Rap1-induced stabilization of endothelial cell--cell junctions.

    abstract::Activation of Rap1 small GTPases stabilizes cell--cell junctions, and this activity requires Krev Interaction Trapped gene 1 (KRIT1). Loss of KRIT1 disrupts cardiovascular development and causes autosomal dominant familial cerebral cavernous malformations. Here we report that native KRIT1 protein binds the effector lo...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E11-02-0157

    authors: Liu JJ,Stockton RA,Gingras AR,Ablooglu AJ,Han J,Bobkov AA,Ginsberg MH

    更新日期:2011-07-15 00:00:00

  • Stabilization of the actomyosin ring enables spermatocyte cytokinesis in Drosophila.

    abstract::The scaffolding protein anillin is required for completion of cytokinesis. Anillin binds filamentous (F) actin, nonmuscle myosin II, and septins and in cell culture models has been shown to restrict actomyosin contractility to the cleavage furrow. Whether anillin also serves this function during the incomplete cytokin...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e09-08-0714

    authors: Goldbach P,Wong R,Beise N,Sarpal R,Trimble WS,Brill JA

    更新日期:2010-05-01 00:00:00

  • Gαq-mediated calcium dynamics and membrane tension modulate neurite plasticity.

    abstract::The formation and disruption of synaptic connections during development are a fundamental step in neural circuit formation. Subneuronal structures such as neurites are known to be sensitive to the level of spontaneous neuronal activity, but the specifics of how neurotransmitter-induced calcium activity regulates neuri...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E19-09-0536

    authors: Pearce KM,Bell M,Linthicum WH,Wen Q,Srinivasan J,Rangamani P,Scarlata S

    更新日期:2020-03-19 00:00:00

  • Dissociation of the Nuf2-Ndc80 complex releases centromeres from the spindle-pole body during meiotic prophase in fission yeast.

    abstract::In the fission yeast Schizosaccharomyces pombe, centromeres remain clustered at the spindle-pole body (SPB) during mitotic interphase. In contrast, during meiotic prophase centromeres dissociate from the SPB. Here we examined the behavior of centromere proteins in living meiotic cells of S. pombe. We show that the Nuf...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e04-11-0996

    authors: Asakawa H,Hayashi A,Haraguchi T,Hiraoka Y

    更新日期:2005-05-01 00:00:00

  • Genetic interactions between the DBL-1/BMP-like pathway and dpy body size-associated genes in Caenorhabditis elegans.

    abstract::Bone morphogenetic protein (BMP) signaling pathways control many developmental and homeostatic processes, including cell size and extracellular matrix remodeling. An understanding of how this pathway itself is controlled remains incomplete. To identify novel regulators of BMP signaling, we performed a forward genetic ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E19-09-0500

    authors: Lakdawala MF,Madhu B,Faure L,Vora M,Padgett RW,Gumienny TL

    更新日期:2019-12-15 00:00:00

  • Cyclin A- and cyclin E-Cdk complexes shuttle between the nucleus and the cytoplasm.

    abstract::Cyclins A and E and their partner cyclin-dependent kinases (Cdks) are key regulators of DNA synthesis and of mitosis. Immunofluorescence studies have shown that both cyclins are nuclear and that a proportion of cyclin A is localized to sites of DNA replication. However, recently, both cyclin A and cyclin E have been i...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.01-07-0361

    authors: Jackman M,Kubota Y,den Elzen N,Hagting A,Pines J

    更新日期:2002-03-01 00:00:00