The Werner Syndrome Helicase Coordinates Sequential Strand Displacement and FEN1-Mediated Flap Cleavage during Polymerase δ Elongation.

Abstract:

:The Werner syndrome protein (WRN) suppresses the loss of telomeres replicated by lagging-strand synthesis by a yet to be defined mechanism. Here, we show that whereas either WRN or the Bloom syndrome helicase (BLM) stimulates DNA polymerase δ progression across telomeric G-rich repeats, only WRN promotes sequential strand displacement synthesis and FEN1 cleavage, a critical step in Okazaki fragment maturation, at these sequences. Helicase activity, as well as the conserved winged-helix (WH) motif and the helicase and RNase D C-terminal (HRDC) domain play important but distinct roles in this process. Remarkably, WRN also influences the formation of FEN1 cleavage products during strand displacement on a nontelomeric substrate, suggesting that WRN recruitment and cooperative interaction with FEN1 during lagging-strand synthesis may serve to regulate sequential strand displacement and flap cleavage at other genomic sites. These findings define a biochemical context for the physiological role of WRN in maintaining genetic stability.

journal_name

Mol Cell Biol

authors

Li B,Reddy S,Comai L

doi

10.1128/MCB.00560-16

subject

Has Abstract

pub_date

2017-01-19 00:00:00

issue

3

eissn

0270-7306

issn

1098-5549

pii

MCB.00560-16

journal_volume

37

pub_type

杂志文章
  • Cyclin-dependent kinase 1-mediated Bcl-xL/Bcl-2 phosphorylation acts as a functional link coupling mitotic arrest and apoptosis.

    abstract::Despite detailed knowledge of the components of the spindle assembly checkpoint, a molecular explanation of how cells die after prolonged spindle checkpoint activation, and thus how microtubule inhibitors and other antimitotic drugs ultimately elicit their lethal effects, has yet to emerge. Mitotically arrested cells ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00882-09

    authors: Terrano DT,Upreti M,Chambers TC

    更新日期:2010-02-01 00:00:00

  • Enhancement of methotrexate resistance and dihydrofolate reductase gene amplification by treatment of mouse 3T6 cells with hydroxyurea.

    abstract::We investigated various parameters associated with the initial selection of mouse 3T6 cells for resistance to single concentrations of methotrexate and characterized resistant colonies for the presence of additional (amplified) copies of the dihydrofolate reductase gene. Our results indicate that the frequency of occu...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.3.6.1097

    authors: Brown PC,Tlsty TD,Schimke RT

    更新日期:1983-06-01 00:00:00

  • Differential regulation of transcription through distinct Suppressor of Hairless DNA binding site architectures during Notch signaling in proneural clusters.

    abstract::In Drosophila melanogaster, achaete (ac) and m8 are model basic helix-loop-helix activator (bHLH A) and repressor genes, respectively, that have the opposite cell expression pattern in proneural clusters during Notch signaling. Previous studies have shown that activation of m8 transcription in specific cells within pr...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00003-10

    authors: Cave JW,Xia L,Caudy M

    更新日期:2011-01-01 00:00:00

  • Human T-cell leukemia virus type 1 Tax induction of NF-kappaB involves activation of the IkappaB kinase alpha (IKKalpha) and IKKbeta cellular kinases.

    abstract::Tax corresponds to a 40-kDa transforming protein from the pathogenic retrovirus human T-cell leukemia virus type 1 (HTLV-1) that activates nuclear expression of the NF-kappaB/Rel family of transcription factors by an unknown mechanism. Tax expression promotes N-terminal phosphorylation and degradation of IkappaB alpha...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.18.9.5157

    authors: Geleziunas R,Ferrell S,Lin X,Mu Y,Cunningham ET Jr,Grant M,Connelly MA,Hambor JE,Marcu KB,Greene WC

    更新日期:1998-09-01 00:00:00

  • Regulation of the nuclear genes encoding the cytoplasmic and mitochondrial leucyl-tRNA synthetases of Neurospora crassa.

    abstract::We show that the nuclear genes for the cytoplasmic and mitochondrial leucyl-tRNA synthetase (LeuRS) of Neurospora crassa are distinct in their encoded proteins, codon usage, mRNA levels, and regulation. The 4.2-kilobase-pair region representing the structural gene for cytoplasmic LeuRS and flanking regions has been se...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.9.11.4645

    authors: Chow CM,Rajbhandary UL

    更新日期:1989-11-01 00:00:00

  • Yeast L double-stranded ribonucleic acid is synthesized during the G1 phase but not the S phase of the cell cycle.

    abstract::The cytoplasm of Saccharomyces cerevisiae contains two major classes of protein-encapsulated double-stranded ribonucleic acids (dsRNA's), L and M. Replication of L and M dsRNA's was examined in cells arrested in the G1 phase by either alpha-factor, a yeast mating pheromone, or the restrictive temperature for a cell cy...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.1.8.673

    authors: Zakian VA,Wagner DW,Fangman WL

    更新日期:1981-08-01 00:00:00

  • The Brn-2 transcription factor links activated BRAF to melanoma proliferation.

    abstract::Malignant melanoma, an aggressive and increasingly common cancer, is characterized by a strikingly high rate (70%) of mutations in BRAF, a key component of the mitogen-activated protein (MAP) kinase signaling pathway. How signaling events downstream from BRAF affect the underlying program of gene expression is poorly ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.24.7.2923-2931.2004

    authors: Goodall J,Wellbrock C,Dexter TJ,Roberts K,Marais R,Goding CR

    更新日期:2004-04-01 00:00:00

  • Differential recruitment of methylated CpG binding domains by the orphan receptor GCNF initiates the repression and silencing of Oct4 expression.

    abstract::The pluripotent factor Oct4 is a key transcription factor that maintains embryonic stem (ES) cell self-renewal and is down-regulated upon the differentiation of ES cells and silenced in somatic cells. A combination of cis elements, transcription factors, and epigenetic modifications, such as DNA methylation, are invol...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章,收录出版

    doi:10.1128/MCB.00898-06

    authors: Gu P,Le Menuet D,Chung AC,Cooney AJ

    更新日期:2006-12-01 00:00:00

  • Formation of tRNA Wobble Inosine in Humans Is Disrupted by a Millennia-Old Mutation Causing Intellectual Disability.

    abstract::The formation of inosine at the wobble position of eukaryotic tRNAs is an essential modification catalyzed by the ADAT2/ADAT3 complex. In humans, a valine-to-methionine mutation (V144M) in ADAT3 that originated ∼1,600 years ago is the most common cause of autosomal recessive intellectual disability (ID) in Arabia. Whi...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00203-19

    authors: Ramos J,Han L,Li Y,Hagelskamp F,Kellner SM,Alkuraya FS,Phizicky EM,Fu D

    更新日期:2019-09-11 00:00:00

  • Regulation of c-Rel nuclear localization by binding of Ca2+/calmodulin.

    abstract::The NF-kappa B/Rel family of transcription factors participates in the control of a wide array of genes, including genes involved in embryonic development and regulation of immune, inflammation, and stress responses. In most cells, inhibitory I kappa B proteins sequester NF-kappa B/Rel in the cytoplasm. Cellular stimu...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.23.4.1418-1427.2003

    authors: Antonsson A,Hughes K,Edin S,Grundström T

    更新日期:2003-02-01 00:00:00

  • The N terminus of Drosophila ESC binds directly to histone H3 and is required for E(Z)-dependent trimethylation of H3 lysine 27.

    abstract::Polycomb group proteins mediate heritable transcriptional silencing and function through multiprotein complexes that methylate and ubiquitinate histones. The 600-kDa E(Z)/ESC complex, also known as Polycomb repressive complex 2 (PRC2), specifically methylates histone H3 lysine 27 (H3 K27) through the intrinsic histone...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01822-06

    authors: Tie F,Stratton CA,Kurzhals RL,Harte PJ

    更新日期:2007-03-01 00:00:00

  • Selective use of ADAM10 and ADAM17 in activation of Notch1 signaling.

    abstract::Notch signaling requires a series of proteolytic cleavage events to release the Notch intracellular domain (NICD) that functions directly in signal transduction. The Notch receptor is locked down in a protease-resistant state by a negative regulatory region (NRR) that protects an ADAM (a disintegrin and metalloproteas...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00406-09

    authors: Bozkulak EC,Weinmaster G

    更新日期:2009-11-01 00:00:00

  • A novel repressor, par-4, modulates transcription and growth suppression functions of the Wilms' tumor suppressor WT1.

    abstract::The tumor suppressor WT1 represses and activates transcription. The loss and/or imbalance of the dual transcriptional activity of WT1 may contribute to Wilms' tumor. In this study, we identified par-4 (for prostate apoptosis response) as a WT1-interacting protein that itself functions as a transcriptional repressor. p...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.16.12.6945

    authors: Johnstone RW,See RH,Sells SF,Wang J,Muthukkumar S,Englert C,Haber DA,Licht JD,Sugrue SP,Roberts T,Rangnekar VM,Shi Y

    更新日期:1996-12-01 00:00:00

  • Genetically essential and nonessential alpha-tubulin genes specify functionally interchangeable proteins.

    abstract::Microtubules in yeast are essential components of the mitotic and meiotic spindles and are essential for nuclear movement during cell division and mating. The relative importance in these processes of the two divergent alpha-tubulin genes of the budding yeast Saccharomyces cerevisiae, TUB1 and TUB3, was examined throu...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.6.11.3722

    authors: Schatz PJ,Solomon F,Botstein D

    更新日期:1986-11-01 00:00:00

  • DNA primase-DNA polymerase alpha from simian cells: sequence specificity of initiation sites on simian virus 40 DNA.

    abstract::Unique single-stranded regions of simian virus 40 DNA, phage M13 virion DNA, and several homopolymers were used as templates for the synthesis of (p)ppRNA-DNA chains by CV-1 cell DNA primase-DNA polymerase alpha. Intact RNA primers, specifically labeled with an RNA capping enzyme, were typically 6 to 8 ribonucleotides...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.5.5.1170

    authors: Yamaguchi M,Hendrickson EA,DePamphilis ML

    更新日期:1985-05-01 00:00:00

  • Inducible expression of chimeric EWS/ETS proteins confers Ewing's family tumor-like phenotypes to human mesenchymal progenitor cells.

    abstract::Ewing's family tumor (EFT) is a rare pediatric tumor of unclear origin that occurs in bone and soft tissue. Specific chromosomal translocations found in EFT cause EWS to fuse to a subset of ets transcription factor genes (ETS), generating chimeric EWS/ETS proteins. These proteins are believed to play a crucial role in...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00740-07

    authors: Miyagawa Y,Okita H,Nakaijima H,Horiuchi Y,Sato B,Taguchi T,Toyoda M,Katagiri YU,Fujimoto J,Hata J,Umezawa A,Kiyokawa N

    更新日期:2008-04-01 00:00:00

  • Tyrosine phosphorylation of the Rho guanine nucleotide exchange factor Trio regulates netrin-1/DCC-mediated cortical axon outgrowth.

    abstract::The chemotropic guidance cue netrin-1 mediates attraction of migrating axons during central nervous system development through the receptor Deleted in Colorectal Cancer (DCC). Downstream of netrin-1, activated Rho GTPases Rac1 and Cdc42 induce cytoskeletal rearrangements within the growth cone. The Rho guanine nucleot...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01264-12

    authors: DeGeer J,Boudeau J,Schmidt S,Bedford F,Lamarche-Vane N,Debant A

    更新日期:2013-02-01 00:00:00

  • Linear distance from the locus control region determines epsilon-globin transcriptional activity.

    abstract::Enhancer elements modulate promoter activity over vast chromosomal distances, and mechanisms that ensure restrictive interactions between promoters and enhancers are critical for proper control of gene expression. The human beta-globin locus control region (LCR) activates expression of five genes in erythroid cells, i...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00602-07

    authors: Shimotsuma M,Matsuzaki H,Tanabe O,Campbell AD,Engel JD,Fukamizu A,Tanimoto K

    更新日期:2007-08-01 00:00:00

  • Characterization of Neurospora CPC1, a bZIP DNA-binding protein that does not require aligned heptad leucines for dimerization.

    abstract::CPC1 is the transcriptional activator of amino acid biosynthetic genes of Neurospora crassa. CPC1 function in vivo was abolished upon deletion of segments of cpc-1 corresponding to the presumed transcription activation domain, the DNA-binding and dimerization domains, or a 52-residue connector segment of CPC1. A trunc...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.11.2.935

    authors: Paluh JL,Yanofsky C

    更新日期:1991-02-01 00:00:00

  • Identification in vivo of different rate-limiting steps associated with transcriptional activators in the presence and absence of a GAGA element.

    abstract::We analyzed the impact of a GAGA element on a transgenic promoter in Drosophila melanogaster that was activated by proteins composed of the Tet(on) DNA binding domain and either the heat shock factor (HSF) activation domain or a potent subdomain of VP16. Permanganate footprinting was used to monitor polymerase II (Pol...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.25.9.3543-3552.2005

    authors: Wang YV,Tang H,Gilmour DS

    更新日期:2005-05-01 00:00:00

  • Selective signaling by Akt1 controls osteoblast differentiation and osteoblast-mediated osteoclast development.

    abstract::Maintaining optimal bone integrity, mass, and strength throughout adult life requires ongoing bone remodeling, which involves coordinated activity between actions of bone-resorbing osteoclasts and bone forming-osteoblasts. Osteoporosis is a disorder of remodeling in which bone resorption outstrips deposition, leading ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.06361-11

    authors: Mukherjee A,Rotwein P

    更新日期:2012-01-01 00:00:00

  • Recognition of CpG island chromatin by KDM2A requires direct and specific interaction with linker DNA.

    abstract::Up to 70% of human genes are associated with regions of nonmethylated DNA called CpG islands (S. Saxonov, P. Berg, and D. L. Brutlag, Proc. Natl. Acad. Sci. U. S. A. 103:1412-1417, 2006). Usually associated with the 5' end of genes, CpG islands are thought to impact gene expression. We previously demonstrated that the...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.06332-11

    authors: Zhou JC,Blackledge NP,Farcas AM,Klose RJ

    更新日期:2012-01-01 00:00:00

  • E2a/Pbx1 induces the rapid proliferation of stem cell factor-dependent murine pro-T cells that cause acute T-lymphoid or myeloid leukemias in mice.

    abstract::Oncoprotein E2a/Pbx1 is produced by the t(1;19) chromosomal translocation of human pre-B acute lymphoblastic leukemia. E2a/Pbx1 blocks differentiation of primary myeloid progenitors but, paradoxically, induces apoptosis in established pre-B-cell lines, and no transforming function of E2a/Pbx1 has been reported in cult...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.24.3.1256-1269.2004

    authors: Sykes DB,Kamps MP

    更新日期:2004-02-01 00:00:00

  • cis- and trans-acting regulatory elements of the yeast URA3 promoter.

    abstract::Expression of the yeast pyrimidine biosynthetic gene, URA3, is induced three- to fivefold in response to uracil starvation, and this regulation is mediated by the transcriptional activator PPR1 (pyrimidine pathway regulator 1). In this study, we have analyzed the regulatory elements of the URA3 promoter by DNase I foo...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.10.10.5257

    authors: Roy A,Exinger F,Losson R

    更新日期:1990-10-01 00:00:00

  • A single-nucleotide polymorphism in a half-binding site creates p53 and estrogen receptor control of vascular endothelial growth factor receptor 1.

    abstract::Interactions between master regulatory pathways provide higher-order controls for cellular regulation. Recently, we reported a C-->T single-nucleotide polymorphism (SNP) in the vascular endothelial growth factor receptor 1 (VEGFR-1/Flt1) promoter that merges human VEGF and p53 pathways. This finding suggested a new la...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01742-06

    authors: Menendez D,Inga A,Snipe J,Krysiak O,Schönfelder G,Resnick MA

    更新日期:2007-04-01 00:00:00

  • Regulation of a senescence checkpoint response by the E2F1 transcription factor and p14(ARF) tumor suppressor.

    abstract::Normal cells do not divide indefinitely due to a process known as replicative senescence. Human cells arrest growth with a senescent phenotype when they acquire one or more critically short telomeres as a consequence of cell division. Recent evidence suggests that certain types of DNA damage, chromatin remodeling, and...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.20.1.273-285.2000

    authors: Dimri GP,Itahana K,Acosta M,Campisi J

    更新日期:2000-01-01 00:00:00

  • ATR1, a Saccharomyces cerevisiae gene encoding a transmembrane protein required for aminotriazole resistance.

    abstract::In Saccharomyces cerevisiae, 3-amino-1,2,4-triazole (aminotriazole) competitively inhibits the activity of imidazoleglycerolphosphate dehydratase, the product of the HIS3 gene. Wild-type strains are able to grow in the presence of 10 mM aminotriazole because they induce the level of imidazoleglycerolphosphate dehydrat...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.8.2.664

    authors: Kanazawa S,Driscoll M,Struhl K

    更新日期:1988-02-01 00:00:00

  • AMPK Promotes Aberrant PGC1β Expression To Support Human Colon Tumor Cell Survival.

    abstract::A major goal of cancer research is the identification of tumor-specific vulnerabilities that can be exploited for the development of therapies that are selectively toxic to the tumor. We show here that the transcriptional coactivators peroxisome proliferator-activated receptor gamma coactivator 1β (PGC1β) and estrogen...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00528-15

    authors: Fisher KW,Das B,Kim HS,Clymer BK,Gehring D,Smith DR,Costanzo-Garvey DL,Fernandez MR,Brattain MG,Kelly DL,MacMillan J,White MA,Lewis RE

    更新日期:2015-11-01 00:00:00

  • Endoplasmic reticulum stress accelerates p53 degradation by the cooperative actions of Hdm2 and glycogen synthase kinase 3beta.

    abstract::Inactivation of the tumor suppressor p53 by degradation is a mechanism utilized by cells to adapt to endoplasmic reticulum (ER) stress. However, the mechanisms of p53 destabilization by ER stress are not known. We demonstrate here that the E3 ubiquitin-ligase Hdm2 is essential for the nucleocytoplasmic transport and p...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.25.21.9392-9405.2005

    authors: Pluquet O,Qu LK,Baltzis D,Koromilas AE

    更新日期:2005-11-01 00:00:00

  • Erk5 participates in neuregulin signal transduction and is constitutively active in breast cancer cells overexpressing ErbB2.

    abstract::The four receptor tyrosine kinases of the ErbB family play essential roles in several physiological processes and have also been implicated in tumor generation and/or progression. Activation of ErbB1/EGFR is mainly triggered by epidermal growth factor (EGF) and other related ligands, while activation of ErbB2, ErbB3, ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.22.1.270-285.2002

    authors: Esparís-Ogando A,Díaz-Rodríguez E,Montero JC,Yuste L,Crespo P,Pandiella A

    更新日期:2002-01-01 00:00:00