53BP1 Mediates ATR-Chk1 Signaling and Protects Replication Forks under Conditions of Replication Stress.

Abstract:

:Complete replication of the genome is an essential prerequisite for normal cell division, but a variety of factors can block the replisome, triggering replication stress and potentially causing mutation or cell death. The cellular response to replication stress involves recruitment of proteins to stabilize the replication fork and transmit a stress signal to pause the cell cycle and allow fork restart. We find that the ubiquitously expressed DNA damage response factor 53BP1 is required for the normal response to replication stress. Using primary, ex vivo B cells, we showed that a population of 53BP1-/- cells in early S phase is hypersensitive to short-term exposure to three different agents that induce replication stress. 53BP1 localizes to a subset of replication forks following induced replication stress, and an absence of 53BP1 leads to defective ATR-Chk1-p53 signaling and caspase 3-mediated cell death. Nascent replicated DNA additionally undergoes degradation in 53BP1-/- cells. These results show that 53BP1 plays an important role in protecting replication forks during the cellular response to replication stress, in addition to the previously characterized role of 53BP1 in DNA double-strand break repair.

journal_name

Mol Cell Biol

authors

Her J,Ray C,Altshuler J,Zheng H,Bunting SF

doi

10.1128/MCB.00472-17

subject

Has Abstract

pub_date

2018-03-29 00:00:00

issue

8

eissn

0270-7306

issn

1098-5549

pii

MCB.00472-17

journal_volume

38

pub_type

杂志文章
  • Factors involved in specific transcription by mammalian RNA polymerase II: purification, genetic specificity, and TATA box-promoter interactions of TFIID.

    abstract::Selective and accurate transcription of purified genes by RNA polymerase II requires multiple factors. The factor designated TFIID was purified extensively from HeLa cell nuclear extracts by using a simple and novel complementation assay. Thus, TFIID was preferentially inactivated by mild heat treatment of a nuclear e...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.8.10.4028

    authors: Nakajima N,Horikoshi M,Roeder RG

    更新日期:1988-10-01 00:00:00

  • Properties of the DNA-binding domain of the simian virus 40 large T antigen.

    abstract::T antigen (Tag) from simian virus 40 binds specifically to two distinct sites in the viral origin of replication and to single-stranded DNA. Analysis of the protein domain responsible for these activities revealed the following. (i) The C-terminal boundary of the origin-specific and single-strand-specific DNA-binding ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.9.12.5525

    authors: McVey D,Strauss M,Gluzman Y

    更新日期:1989-12-01 00:00:00

  • Essential role for mitochondrial thioredoxin reductase in hematopoiesis, heart development, and heart function.

    abstract::Oxygen radicals regulate many physiological processes, such as signaling, proliferation, and apoptosis, and thus play a pivotal role in pathophysiology and disease development. There are at least two thioredoxin reductase/thioredoxin/peroxiredoxin systems participating in the cellular defense against oxygen radicals. ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.24.21.9414-9423.2004

    authors: Conrad M,Jakupoglu C,Moreno SG,Lippl S,Banjac A,Schneider M,Beck H,Hatzopoulos AK,Just U,Sinowatz F,Schmahl W,Chien KR,Wurst W,Bornkamm GW,Brielmeier M

    更新日期:2004-11-01 00:00:00

  • Generation and analysis of mice lacking the chemokine fractalkine.

    abstract::Fractalkine (CX(3)CL1) is the first described chemokine that can exist either as a soluble protein or as a membrane-bound molecule. Both forms of fractalkine can mediate adhesion of cells expressing its receptor, CX(3)CR1. This activity, together with its expression on endothelial cells, suggests that fractalkine migh...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.21.9.3159-3165.2001

    authors: Cook DN,Chen SC,Sullivan LM,Manfra DJ,Wiekowski MT,Prosser DM,Vassileva G,Lira SA

    更新日期:2001-05-01 00:00:00

  • The myc intron-binding polypeptide associates with RFX1 in vivo and binds to the major histocompatibility complex class II promoter region, to the hepatitis B virus enhancer, and to regulatory regions of several distinct viral genes.

    abstract::We demonstrated that MIF-1, identified initially as a binding activity that associated with the intron I element of the c-myc gene, consists of two polypeptides, the myc intron-binding peptide (MIBP1) and the major histocompatibility class II promoter-binding protein, RFX1. Using a polyclonal antiserum directed agains...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.15.6.3041

    authors: Reinhold W,Emens L,Itkes A,Blake M,Ichinose I,Zajac-Kaye M

    更新日期:1995-06-01 00:00:00

  • Organization of a Chinese hamster ovary dihydrofolate reductase gene identified by phenotypic rescue.

    abstract::We have constructed a genomic DNA library from a methotrexate-resistant Chinese hamster ovary cell line (CHOC 400) in the cosmid vector pHC79. By utilizing a murine dihydrofolate reductase (DHFR) cDNA clone, we have identified 66 DHFR+ clones among the 11,000 colonies screened by colony hybridization. To isolate a rec...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.3.7.1266

    authors: Milbrandt JD,Azizkhan JC,Greisen KS,Hamlin JL

    更新日期:1983-07-01 00:00:00

  • The immunoglobulin heavy-chain enhancer functions as the promoter for I mu sterile transcription.

    abstract::We demonstrate that the immunoglobulin heavy-chain enhancer functions as the promoter for I mu sterile transcription. The enhancer itself, when placed 5' to the bacterial cat or neo genes, is able to direct transcription by using heterogeneous start sites that are generally the same as those found with bona fide I mu ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.10.6.2619

    authors: Su LK,Kadesch T

    更新日期:1990-06-01 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

  • Cooperation of six and eya in activation of their target genes through nuclear translocation of Eya.

    abstract::Drosophila sine oculis and eyes absent genes synergize in compound-eye formation. The murine homologues of these genes, Six and Eya, respectively, show overlapping expression patterns during development. We hypothesized that Six and Eya proteins cooperate to regulate their target genes. Cotransfection assays were perf...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.19.10.6815

    authors: Ohto H,Kamada S,Tago K,Tominaga SI,Ozaki H,Sato S,Kawakami K

    更新日期:1999-10-01 00:00:00

  • Interleukin-6- and leukemia inhibitory factor-induced terminal differentiation of myeloid leukemia cells is blocked at an intermediate stage by constitutive c-myc.

    abstract::Interleukin-6 (IL-6) and leukemia inhibitory factor (LIF), two multifunctional cytokines, recently have been identified as physiological inducers of hematopoietic cell differentiation which also induce terminal differentiation and growth arrest of the myeloblastic leukemic M1 cell line. In this work, it is shown that ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.11.5.2375

    authors: Hoffman-Liebermann B,Liebermann DA

    更新日期:1991-05-01 00:00:00

  • Cloning and characterization of two novel thyroid hormone receptor beta isoforms.

    abstract::Thyroid hormone (T(3)) activates nuclear receptor transcription factors, encoded by the TRalpha (NR1A1) and TRbeta (NR1A2) genes, to regulate target gene expression. Several TR isoforms exist, and studies of null mice have identified some unique functions for individual TR variants, although considerable redundancy oc...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.20.22.8329-8342.2000

    authors: Williams GR

    更新日期:2000-11-01 00:00:00

  • Identification of a signal for nuclear targeting in platelet-derived-growth-factor-related molecules.

    abstract::The v-vis gene encodes p28sis, the transforming protein of simian sarcoma virus. This gene resulted from a fusion of the env gene of simian sarcoma-associated virus and the woolly monkey gene for the B chain of platelet-derived growth factor (PDGF). Previous work has shown that the v-sis gene product undergoes signal ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.7.10.3527

    authors: Lee BA,Maher DW,Hannink M,Donoghue DJ

    更新日期:1987-10-01 00:00:00

  • RNA Binding by Histone Methyltransferases Set1 and Set2.

    abstract::Histone methylation at H3K4 and H3K36 is commonly associated with genes actively transcribed by RNA polymerase II (RNAPII) and is catalyzed by Saccharomyces cerevisiae Set1 and Set2, respectively. Here we report that both methyltransferases can be UV cross-linked to RNA in vivo High-throughput sequencing of the bound ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00165-17

    authors: Sayou C,Millán-Zambrano G,Santos-Rosa H,Petfalski E,Robson S,Houseley J,Kouzarides T,Tollervey D

    更新日期:2017-06-29 00:00:00

  • mRNA instability in the nucleus due to a novel open reading frame element is a major determinant of the narrow tissue specificity of folate receptor alpha.

    abstract::The folate receptor type alpha (FR-alpha) is a promising tumor marker and target. Here, we investigate the mechanistic basis for the tumor specificity and vast overexpression of FR-alpha. Among representative FR-alpha-positive (HeLa and JAR) and FR-alpha-negative (MG63, Caki1, and HT3) cell lines, the transcription ra...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.23.6.2202-2212.2003

    authors: Zheng X,Kelley K,Elnakat H,Yan W,Dorn T,Ratnam M

    更新日期:2003-03-01 00:00:00

  • Role of gene order in developmental control of human gamma- and beta-globin gene expression.

    abstract::To determine the effect of gene order on globin gene developmental regulation, we produced transgenic mice containing two tandemly arranged gamma- or beta-globin or gamma beta- and beta gamma-globin genes linked to a 2.5-kb cassette containing sequences of the locus control region (LCR). Analysis of constructs contain...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.13.8.4836

    authors: Peterson KR,Stamatoyannopoulos G

    更新日期:1993-08-01 00:00:00

  • Replication past O(6)-methylguanine by yeast and human DNA polymerase eta.

    abstract::O(6)-Methylguanine (m6G) is formed by the action of alkylating agents such as N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) on DNA. m6G is a highly mutagenic and carcinogenic lesion, and it presents a block to synthesis by DNA polymerases. Here, we provide genetic and biochemical evidence for the involvement of yeast an...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.20.21.8001-8007.2000

    authors: Haracska L,Prakash S,Prakash L

    更新日期:2000-11-01 00:00:00

  • Genetic and biochemical distinction among Chinese hamster cell emtA, emtB, and emtC mutants.

    abstract::Genetic and biochemical experiments have enabled us to more clearly distinguish three genetic loci, emtA, emtB, and emtC, all of which can be altered to give rise to resistance to the protein synthesis inhibitor, emetine, in cultured Chinese hamster cells. Genetic experiments have demonstrated that, unlike the emtB lo...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.3.3.429

    authors: Chang S,Wasmuth JJ

    更新日期:1983-03-01 00:00:00

  • Expression of HLA-DR antigen in human class II mutant B-cell lines by double infection with retrovirus vectors.

    abstract::A new retrovirus vector containing the gene for hygromycin B resistance (hyg) as a selectable marker under the control of an internal simian virus 40 promoter was constructed. It was used, together with an analogous previously described vector, DO1, which contains the gene for G418 resistance, to introduce and express...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.7.11.3923

    authors: Yang Z,Korman AJ,Cooper J,Pious D,Accolla RS,Mulligan RC,Strominger JL

    更新日期:1987-11-01 00:00:00

  • Silencing of Wnt signaling and activation of multiple metabolic pathways in response to thyroid hormone-stimulated cell proliferation.

    abstract::To investigate the transcriptional program underlying thyroid hormone (T3)-induced cell proliferation, cDNA microarrays were used to survey the temporal expression profiles of 4,400 genes. Of 358 responsive genes identified, 88% had not previously been reported to be transcriptionally or functionally modulated by T3. ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.21.19.6626-6639.2001

    authors: Miller LD,Park KS,Guo QM,Alkharouf NW,Malek RL,Lee NH,Liu ET,Cheng SY

    更新日期:2001-10-01 00:00:00

  • Disruption of spermatogenic cell adhesion and male infertility in mice lacking TSLC1/IGSF4, an immunoglobulin superfamily cell adhesion molecule.

    abstract::TSLC1/IGSF4, an immunoglobulin superfamily molecule, is predominantly expressed in the brain, lungs, and testes and plays important roles in epithelial cell adhesion, cancer invasion, and synapse formation. We generated Tslc1/Igsf4-deficient mice by disrupting exon 1 of the gene and found that Tslc1(-/-) mice were bor...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.26.9.3610-3624.2006

    authors: Yamada D,Yoshida M,Williams YN,Fukami T,Kikuchi S,Masuda M,Maruyama T,Ohta T,Nakae D,Maekawa A,Kitamura T,Murakami Y

    更新日期:2006-05-01 00:00:00

  • Topology and functional domains of Sec63p, an endoplasmic reticulum membrane protein required for secretory protein translocation.

    abstract::SEC63 encodes a protein required for secretory protein translocation into the endoplasmic reticulum (ER) of Saccharomyces cerevisiae (J. A. Rothblatt, R. J. Deshaies, S. L. Sanders, G. Daum, and R. Schekman, J. Cell Biol. 109:2641-2652, 1989). Antibody directed against a recombinant form of the protein detects a 73-kD...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.12.7.3288

    authors: Feldheim D,Rothblatt J,Schekman R

    更新日期:1992-07-01 00:00:00

  • Guanine nucleotide activation of, and competition between, RAS proteins from Saccharomyces cerevisiae.

    abstract::In the yeast Saccharomyces cerevisiae, yeast RAS proteins are potent activators of adenylate cyclase. In the present work we measured the activity of adenylate cyclase in membranes from Saccharomyces cerevisiae which overexpress this enzyme. The response of the enzyme to added RAS2 proteins bound with various guanine ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.7.6.2128

    authors: Field J,Broek D,Kataoka T,Wigler M

    更新日期:1987-06-01 00:00:00

  • Regulation of MyD88-dependent signaling events by S nitrosylation retards toll-like receptor signal transduction and initiation of acute-phase immune responses.

    abstract::Nitric oxide (NO) has been thought to regulate the immune system through S nitrosylation of the transcriptional factor NF-kappaB. However, regulatory effects of NO on innate immune responses are unclear. Here, we report that NO has a capability to control Toll-like receptor-mediated signaling through S nitrosylation. ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01412-07

    authors: Into T,Inomata M,Nakashima M,Shibata K,Häcker H,Matsushita K

    更新日期:2008-02-01 00:00:00

  • Nucleotide sequences required for the regulation of a rat alpha 2u-globulin gene by glucocorticoids.

    abstract::alpha 2u-Globulin is a rat protein of as yet unknown function whose synthesis can be induced by glucocorticoids and several other hormones. Induction by glucocorticoids is a secondary response to the hormone: protein synthesis is required before the hormone can exert its stimulatory effect on alpha 2u-globulin transcr...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.6.7.2334

    authors: Addison WR,Kurtz DT

    更新日期:1986-07-01 00:00:00

  • Functional asymmetry of the regions juxtaposed to the membrane-binding sequence of polyomavirus middle T antigen.

    abstract::The functional importance of the two clusters of positively charged amino acids which flank the hydrophobic membrane-anchoring sequence of polyomavirus middle T (mT) protein has been investigated by using site-directed mutagenesis. A clear asymmetry was apparent. No effect on transformation was seen following multiple...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.12.11.5050

    authors: Dahl J,Thathamangalam U,Freund R,Benjamin TL

    更新日期:1992-11-01 00:00:00

  • Hierarchy of protein tyrosine kinases in interleukin-2 (IL-2) signaling: activation of syk depends on Jak3; however, neither Syk nor Lck is required for IL-2-mediated STAT activation.

    abstract::Interleukin-2 (IL-2) activates several different families of tyrosine kinases, but precisely how these kinases interact is not completely understood. We therefore investigated the functional relationships among Jak3, Lck, and Syk in IL-2 signaling. We first observed that in the absence of Jak3, both Lck and Syk had th...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.20.12.4371-4380.2000

    authors: Zhou YJ,Magnuson KS,Cheng TP,Gadina M,Frucht DM,Galon J,Candotti F,Geahlen RL,Changelian PS,O'Shea JJ

    更新日期:2000-06-01 00:00:00

  • The natural osmolyte trehalose is a positive regulator of the heat-induced activity of yeast heat shock transcription factor.

    abstract::In Saccharomyces cerevisiae, the intracellular concentration of trehalose increases rapidly in response to many environmental stresses, including heat shock. These high trehalose levels have been correlated with tolerance to adverse conditions and led to the model that trehalose functions as a chemical cochaperone. He...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01158-06

    authors: Conlin LK,Nelson HC

    更新日期:2007-02-01 00:00:00

  • Identification and partial characterization of an extracellular acid phosphatase activity of Leishmania donovani promastigotes.

    abstract::An extracellular acid phosphatase was detected in the growth media of Leishmania donovani promastigotes. The enzyme was released at all stages of the growth cycle and in amounts which accounted for 90% of the total amount of this enzyme in the culture. The exoenzyme exhibited a pH optimum of 4.5 to 5.0 and was active ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.2.1.76

    authors: Gottlieb M,Dwyer DM

    更新日期:1982-01-01 00:00:00

  • Effects of epidermal growth factor and 12-O-tetradecanoylphorbol-13-acetate on metabolism of the epidermal growth factor receptor in normal human fibroblasts.

    abstract::The biosynthesis, phosphorylation, and degradation of the epidermal growth factor (EGF) receptor were examined in normal human fibroblasts. The receptor was initially synthesized as an Mr = 160,000 immature form which matured to an Mr = 170,000 form in a monensin-sensitive manner. Tunicamycin treatment led to the accu...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.4.9.1718

    authors: Decker SJ

    更新日期:1984-09-01 00:00:00

  • Activation of a late H2B histone gene in blastula-stage sea urchin embryos by an unusual enhancer element located 3' of the gene.

    abstract::In the sea urchin embryo, late histone genes are transcribed at low levels during cleavage and blastula formation and at substantially higher levels in later stages of embryogenesis. To investigate the molecular basis of the stage-specific expression of a late H2B histone gene, we injected mutant genes lacking portion...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.10.12.6730

    authors: Zhao AZ,Colin AM,Bell J,Baker M,Char BR,Maxson R

    更新日期:1990-12-01 00:00:00