ATR kinase activation mediated by MutSalpha and MutLalpha in response to cytotoxic O6-methylguanine adducts.


:S(N)1-type alkylating agents that produce cytotoxic O(6)-methyl-G (O(6)-meG) DNA adducts induce cell cycle arrest and apoptosis in a manner requiring the DNA mismatch repair (MMR) proteins MutSalpha and MutLalpha. Here, we show that checkpoint signaling in response to DNA methylation occurs during S phase and requires DNA replication that gives rise to O(6)-meG/T mispairs. DNA binding studies reveal that MutSalpha specifically recognizes O(6)-meG/T mispairs, but not O(6)-meG/C. In an in vitro assay, ATR-ATRIP, but not RPA, is preferentially recruited to O(6)-meG/T mismatches in a MutSalpha- and MutLalpha-dependent manner. Furthermore, ATR kinase is activated to phosphorylate Chk1 in the presence of O(6)-meG/T mispairs and MMR proteins. These results suggest that MMR proteins can act as direct sensors of methylation damage and help recruit ATR-ATRIP to sites of cytotoxic O(6)-meG adducts to initiate ATR checkpoint signaling.


Mol Cell


Molecular cell


Yoshioka K,Yoshioka Y,Hsieh P




Has Abstract


2006-05-19 00:00:00














  • A pre-ribosome with a tadpole-like structure functions in ATP-dependent maturation of 60S subunits.

    abstract::Analyses of isolated pre-ribosomes yielded biochemical "snapshots" of the dynamic, nascent 60S and 40S subunits during their path from the nucleolus to the cytoplasm. Here, we present the structure of a pre-60S ribosomal intermediate located in the nucleoplasm. A huge dynein-related AAA-type ATPase (Rea1) and the Rix1...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Nissan TA,Galani K,Maco B,Tollervey D,Aebi U,Hurt E

    更新日期:2004-07-23 00:00:00

  • Mph1 and Mus81-Mms4 prevent aberrant processing of mitotic recombination intermediates.

    abstract::Homology-dependent repair of double-strand breaks (DSBs) from nonsister templates has the potential to generate loss of heterozygosity or genome rearrangements. Here we show that the Saccharomyces cerevisiae Mph1 helicase prevents crossovers between ectopic sequences by removing substrates for Mus81-Mms4 or Rad1-Rad10...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Mazón G,Symington LS

    更新日期:2013-10-10 00:00:00

  • Transcriptional ShortCUTs.

    abstract::Recent work from Kuehner and Brow (2008) and Thiebaut et al. (2008) in Molecular Cell and Jenks et al. (2008) in Molecular and Cellular Biology reveals that regulated expression of central nucleotide synthesis pathway components directs start site-dependent RNA polymerase II termination. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章


    authors: Dichtl B

    更新日期:2008-09-05 00:00:00

  • A role for the deep orange and carnation eye color genes in lysosomal delivery in Drosophila.

    abstract::Deep orange and carnation are two of the classic eye color genes in Drosophila. Here, we demonstrate that Deep orange is part of a protein complex that localizes to endosomal compartments. A second component of this complex is Carnation, a homolog of Sec1p-like regulators of membrane fusion. Because complete loss of d...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Sevrioukov EA,He JP,Moghrabi N,Sunio A,Krämer H

    更新日期:1999-10-01 00:00:00

  • Mitotic Transcription Installs Sgo1 at Centromeres to Coordinate Chromosome Segregation.

    abstract::Human sister chromatids at metaphase are primarily linked by centromeric cohesion, forming the iconic X shape. Premature loss of centromeric cohesion disrupts orderly mitotic progression. Shugoshin (Sgo1) binds to and protects cohesin at inner centromeres. The kinetochore kinase Bub1 phosphorylates histone H2A at T120...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Liu H,Qu Q,Warrington R,Rice A,Cheng N,Yu H

    更新日期:2015-08-06 00:00:00

  • Angiogenin-induced tRNA fragments inhibit translation initiation.

    abstract::Angiogenin is a stress-activated ribonuclease that cleaves tRNA within anticodon loops to produce tRNA-derived stress-induced fragments (tiRNAs). Transfection of natural or synthetic tiRNAs inhibits protein synthesis and triggers the phospho-eIF2α-independent assembly of stress granules (SGs), essential components of ...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Ivanov P,Emara MM,Villen J,Gygi SP,Anderson P

    更新日期:2011-08-19 00:00:00

  • AMPK phosphorylation of raptor mediates a metabolic checkpoint.

    abstract::AMPK is a highly conserved sensor of cellular energy status that is activated under conditions of low intracellular ATP. AMPK responds to energy stress by suppressing cell growth and biosynthetic processes, in part through its inhibition of the rapamycin-sensitive mTOR (mTORC1) pathway. AMPK phosphorylation of the TSC...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Gwinn DM,Shackelford DB,Egan DF,Mihaylova MM,Mery A,Vasquez DS,Turk BE,Shaw RJ

    更新日期:2008-04-25 00:00:00

  • R-Loop Mediated trans Action of the APOLO Long Noncoding RNA.

    abstract::In eukaryotes, three-dimensional genome organization is critical for transcriptional regulation of gene expression. Long noncoding RNAs (lncRNAs) can modulate chromatin conformation of spatially related genomic locations within the nucleus. Here, we show that the lncRNA APOLO (AUXIN-REGULATED PROMOTER LOOP) recognizes...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Ariel F,Lucero L,Christ A,Mammarella MF,Jegu T,Veluchamy A,Mariappan K,Latrasse D,Blein T,Liu C,Benhamed M,Crespi M

    更新日期:2020-03-05 00:00:00

  • Autoadaptive ER-associated degradation defines a preemptive unfolded protein response pathway.

    abstract::Folding-defective proteins must be cleared efficiently from the endoplasmic reticulum (ER) to prevent perturbation of the folding environment and to maintain cellular proteostasis. Misfolded proteins engage dislocation machineries (dislocons) built around E3 ubiquitin ligases that promote their transport across the ER...

    journal_title:Molecular cell

    pub_type: 杂志文章,收录出版


    authors: Bernasconi R,Galli C,Kokame K,Molinari M

    更新日期:2013-12-26 00:00:00

  • Structures of Neisseria meningitidis Cas9 Complexes in Catalytically Poised and Anti-CRISPR-Inhibited States.

    abstract::High-resolution Cas9 structures have yet to reveal catalytic conformations due to HNH nuclease domain positioning away from the cleavage site. Nme1Cas9 and Nme2Cas9 are compact nucleases for in vivo genome editing. Here, we report structures of meningococcal Cas9 homologs in complex with sgRNA, dsDNA, or the AcrIIC3 a...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Sun W,Yang J,Cheng Z,Amrani N,Liu C,Wang K,Ibraheim R,Edraki A,Huang X,Wang M,Wang J,Liu L,Sheng G,Yang Y,Lou J,Sontheimer EJ,Wang Y

    更新日期:2019-12-19 00:00:00

  • The F-box Protein KIB1 Mediates Brassinosteroid-Induced Inactivation and Degradation of GSK3-like Kinases in Arabidopsis.

    abstract::The glycogen synthase kinase-3 (GSK3) family kinases are central cellular regulators highly conserved in all eukaryotes. In Arabidopsis, the GSK3-like kinase BIN2 phosphorylates a range of proteins to control broad developmental processes, and BIN2 is degraded through unknown mechanism upon receptor kinase-mediated br...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Zhu JY,Li Y,Cao DM,Yang H,Oh E,Bi Y,Zhu S,Wang ZY

    更新日期:2017-06-01 00:00:00

  • Structural analysis of engineered Bb fragment of complement factor B: insights into the activation mechanism of the alternative pathway C3-convertase.

    abstract::The C-terminal fragment, Bb, of factor B combines with C3b to form the pivotal C3-convertase, C3bBb, of alternative complement pathway. Bb consists of a von Willebrand factor type A (vWFA) domain that is structurally similar to the I domains of integrins and a serine protease (SP) domain that is in inactive conformati...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Ponnuraj K,Xu Y,Macon K,Moore D,Volanakis JE,Narayana SV

    更新日期:2004-04-09 00:00:00

  • HDAC6 modulates cell motility by altering the acetylation level of cortactin.

    abstract::Histone deacetylase 6 (HDAC6) is a tubulin-specific deacetylase that regulates microtubule-dependent cell movement. In this study, we identify the F-actin-binding protein cortactin as a HDAC6 substrate. We demonstrate that HDAC6 binds cortactin and that overexpression of HDAC6 leads to hypoacetylation of cortactin, wh...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Zhang X,Yuan Z,Zhang Y,Yong S,Salas-Burgos A,Koomen J,Olashaw N,Parsons JT,Yang XJ,Dent SR,Yao TP,Lane WS,Seto E

    更新日期:2007-07-20 00:00:00

  • MCM8- and MCM9-deficient mice reveal gametogenesis defects and genome instability due to impaired homologous recombination.

    abstract::We generated knockout mice for MCM8 and MCM9 and show that deficiency for these genes impairs homologous recombination (HR)-mediated DNA repair during gametogenesis and somatic cells cycles. MCM8(-/-) mice are sterile because spermatocytes are blocked in meiotic prophase I, and females have only arrested primary folli...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Lutzmann M,Grey C,Traver S,Ganier O,Maya-Mendoza A,Ranisavljevic N,Bernex F,Nishiyama A,Montel N,Gavois E,Forichon L,de Massy B,Méchali M

    更新日期:2012-08-24 00:00:00

  • APC is essential for targeting phosphorylated beta-catenin to the SCFbeta-TrCP ubiquitin ligase.

    abstract::Ubiquitin-dependent proteolysis is an important mechanism that suppresses the beta-catenin transcription factor in cells without Wnt stimulation. A critical step in this regulatory pathway is to create a SCF(beta-TrCP) E3 ubiquitin ligase binding site for beta-catenin. Here we show that the SCF(beta-TrCP) binding site...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Su Y,Fu C,Ishikawa S,Stella A,Kojima M,Shitoh K,Schreiber EM,Day BW,Liu B

    更新日期:2008-12-05 00:00:00

  • PKR Senses Nuclear and Mitochondrial Signals by Interacting with Endogenous Double-Stranded RNAs.

    abstract::Protein kinase RNA-activated (PKR) induces immune response by sensing viral double-stranded RNAs (dsRNAs). However, growing evidence suggests that PKR can also be activated by endogenously expressed dsRNAs. Here, we capture these dsRNAs by formaldehyde-mediated crosslinking and immunoprecipitation sequencing and find ...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Kim Y,Park J,Kim S,Kim M,Kang MG,Kwak C,Kang M,Kim B,Rhee HW,Kim VN

    更新日期:2018-09-20 00:00:00

  • Gemin5 delivers snRNA precursors to the SMN complex for snRNP biogenesis.

    abstract::The SMN complex assembles Sm cores on snRNAs, a key step in the biogenesis of snRNPs, the spliceosome's major components. Here, using SMN complex inhibitors identified by high-throughput screening and a ribo-proteomic strategy on formaldehyde crosslinked RNPs, we dissected this pathway in cells. We show that protein s...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Yong J,Kasim M,Bachorik JL,Wan L,Dreyfuss G

    更新日期:2010-05-28 00:00:00

  • The structure of SOCS3 reveals the basis of the extended SH2 domain function and identifies an unstructured insertion that regulates stability.

    abstract::SOCS3 is essential for regulating the extent, duration, and specificity of cellular responses to cytokines such as G-CSF and IL-6. Here we describe the solution structure of SOCS3, the first structure determined for any SOCS protein, in complex with a phosphotyrosine-containing peptide from the IL-6 receptor signaling...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Babon JJ,McManus EJ,Yao S,DeSouza DP,Mielke LA,Sprigg NS,Willson TA,Hilton DJ,Nicola NA,Baca M,Nicholson SE,Norton RS

    更新日期:2006-04-21 00:00:00

  • Exploration of the topological requirements of ERAD identifies Yos9p as a lectin sensor of misfolded glycoproteins in the ER lumen.

    abstract::ER-associated degradation (ERAD) of glycoproteins depends on dual recognition of protein misfolding and remodeling of the substrate's N-linked glycans. After recognition, substrates are retrotranslocated to the cytosol for proteasomal degradation. To explore the directionality of this process, we fused a highly stable...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Bhamidipati A,Denic V,Quan EM,Weissman JS

    更新日期:2005-09-16 00:00:00

  • Systematic Gene-to-Phenotype Arrays: A High-Throughput Technique for Molecular Phenotyping.

    abstract::We have developed a highly parallel strategy, systematic gene-to-phenotype arrays (SGPAs), to comprehensively map the genetic landscape driving molecular phenotypes of interest. By this approach, a complete yeast genetic mutant array is crossed with fluorescent reporters and imaged on membranes at high density and con...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Jaeger PA,Ornelas L,McElfresh C,Wong LR,Hampton RY,Ideker T

    更新日期:2018-01-18 00:00:00

  • A basal promoter element recognized by free RNA polymerase sigma subunit determines promoter recognition by RNA polymerase holoenzyme.

    abstract::During transcription initiation by bacterial RNA polymerase, the sigma subunit recognizes the -35 and -10 promoter elements; free sigma, however, does not bind DNA. We selected ssDNA aptamers that strongly and specifically bound free sigma(A) from Thermus aquaticus. A consensus sequence, GTA(C/T)AATGGGA, was required ...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Feklistov A,Barinova N,Sevostyanova A,Heyduk E,Bass I,Vvedenskaya I,Kuznedelov K,Merkiene E,Stavrovskaya E,Klimasauskas S,Nikiforov V,Heyduk T,Severinov K,Kulbachinskiy A

    更新日期:2006-07-07 00:00:00

  • Formation of an IKKalpha-dependent transcription complex is required for estrogen receptor-mediated gene activation.

    abstract::The IkappaB kinases IKKalpha and IKKbeta regulate distinct cytoplasmic and nuclear events that are critical for cytokine-mediated activation of the NF-kappaB pathway. Because the IKKs have previously been demonstrated to associate with the nuclear hormone receptor coactivator AIB1/SRC-3, the question of whether either...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Park KJ,Krishnan V,O'Malley BW,Yamamoto Y,Gaynor RB

    更新日期:2005-04-01 00:00:00

  • High-Resolution Mapping of Multiway Enhancer-Promoter Interactions Regulating Pathogen Detection.

    abstract::Eukaryotic gene expression regulation involves thousands of distal regulatory elements. Understanding the quantitative contribution of individual enhancers to gene expression is critical for assessing the role of disease-associated genetic risk variants. Yet, we lack the ability to accurately link genes with their dis...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Vangala P,Murphy R,Quinodoz SA,Gellatly K,McDonel P,Guttman M,Garber M

    更新日期:2020-10-15 00:00:00

  • Acetylation Enhances TET2 Function in Protecting against Abnormal DNA Methylation during Oxidative Stress.

    abstract::TET proteins, by converting 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), are hypothesized, but not directly shown, to protect promoter CpG islands (CGIs) against abnormal DNA methylation (DNAm) in cancer. We define such a protective role linked to DNA damage from oxidative stress (OS) known to induce this...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Zhang YW,Wang Z,Xie W,Cai Y,Xia L,Easwaran H,Luo J,Yen RC,Li Y,Baylin SB

    更新日期:2017-01-19 00:00:00

  • Yng1 PHD finger binding to H3 trimethylated at K4 promotes NuA3 HAT activity at K14 of H3 and transcription at a subset of targeted ORFs.

    abstract::Posttranslational histone modifications participate in modulating the structure and function of chromatin. Promoters of transcribed genes are enriched with K4 trimethylation and hyperacetylation on the N-terminal tail of histone H3. Recently, PHD finger proteins, like Yng1 in the NuA3 HAT complex, were shown to intera...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Taverna SD,Ilin S,Rogers RS,Tanny JC,Lavender H,Li H,Baker L,Boyle J,Blair LP,Chait BT,Patel DJ,Aitchison JD,Tackett AJ,Allis CD

    更新日期:2006-12-08 00:00:00

  • Caspase-2-mediated cleavage of Mdm2 creates a p53-induced positive feedback loop.

    abstract::Caspase-2 is an evolutionarily conserved caspase, yet its biological function and cleavage targets are poorly understood. Caspase-2 is activated by the p53 target gene product PIDD (also known as LRDD) in a complex called the Caspase-2-PIDDosome. We show that PIDD expression promotes growth arrest and chemotherapy res...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Oliver TG,Meylan E,Chang GP,Xue W,Burke JR,Humpton TJ,Hubbard D,Bhutkar A,Jacks T

    更新日期:2011-07-08 00:00:00

  • Extracellular adenosine sensing-a metabolic cell death priming mechanism downstream of p53.

    abstract::Tumor cells undergo changes in metabolism to meet their energetic and anabolic needs. It is conceivable that mechanisms exist to sense these changes and link them to pathways that eradicate cells primed for cancer development. We report that the tumor suppressor p53 activates a cell death priming mechanism that senses...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Long JS,Crighton D,O'Prey J,Mackay G,Zheng L,Palmer TM,Gottlieb E,Ryan KM

    更新日期:2013-05-09 00:00:00

  • Hierarchical modularity and the evolution of genetic interactomes across species.

    abstract::To date, cross-species comparisons of genetic interactomes have been restricted to small or functionally related gene sets, limiting our ability to infer evolutionary trends. To facilitate a more comprehensive analysis, we constructed a genome-scale epistasis map (E-MAP) for the fission yeast Schizosaccharomyces pombe...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Ryan CJ,Roguev A,Patrick K,Xu J,Jahari H,Tong Z,Beltrao P,Shales M,Qu H,Collins SR,Kliegman JI,Jiang L,Kuo D,Tosti E,Kim HS,Edelmann W,Keogh MC,Greene D,Tang C,Cunningham P,Shokat KM,Cagney G,Svensson JP,Gut

    更新日期:2012-06-08 00:00:00

  • Diverse pathways generate microRNA-like RNAs and Dicer-independent small interfering RNAs in fungi.

    abstract::A variety of small RNAs, including the Dicer-dependent miRNAs and the Dicer-independent Piwi-interacting RNAs, associate with Argonaute family proteins to regulate gene expression in diverse cellular processes. These two species of small RNA have not been found in fungi. Here, by analyzing small RNAs associated with t...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Lee HC,Li L,Gu W,Xue Z,Crosthwaite SK,Pertsemlidis A,Lewis ZA,Freitag M,Selker EU,Mello CC,Liu Y

    更新日期:2010-06-25 00:00:00

  • Adaptation in CRISPR-Cas Systems.

    abstract::Clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) proteins constitute an adaptive immune system in prokaryotes. The system preserves memories of prior infections by integrating short segments of foreign DNA, termed spacers, into the CRISPR array in a process termed adaptati...

    journal_title:Molecular cell

    pub_type: 杂志文章,评审


    authors: Sternberg SH,Richter H,Charpentier E,Qimron U

    更新日期:2016-03-17 00:00:00