Dynamics of DNA damage response proteins at DNA breaks: a focus on protein modifications.


:Genome integrity is constantly monitored by sophisticated cellular networks, collectively termed the DNA damage response (DDR). A common feature of DDR proteins is their mobilization in response to genotoxic stress. Here, we outline how the development of various complementary methodologies has provided valuable insights into the spatiotemporal dynamics of DDR protein assembly/disassembly at sites of DNA strand breaks in eukaryotic cells. Considerable advances have also been made in understanding the underlying molecular mechanisms for these events, with post-translational modifications of DDR factors being shown to play prominent roles in controlling the formation of foci in response to DNA-damaging agents. We review these regulatory mechanisms and discuss their biological significance to the DDR.


Genes Dev


Genes & development


Polo SE,Jackson SP




Has Abstract


2011-03-01 00:00:00














  • Hematopoietic development of embryonic stem cells in vitro: cytokine and receptor gene expression.

    abstract::A novel system to study early hematopoietic development is described. This report documents the in vitro capacity of murine embryonic stem (ES) cells to differentiate into hematopoietic precursors of most, if not all, of the colony-forming cells found in normal bone marrow. This system is used to correlate the genetic...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Schmitt RM,Bruyns E,Snodgrass HR

    更新日期:1991-05-01 00:00:00

  • Analysis of lung tumor initiation and progression using conditional expression of oncogenic K-ras.

    abstract::Adenocarcinoma of the lung is the most common form of lung cancer, but the cell of origin and the stages of progression of this tumor type are not well understood. We have developed a new model of lung adenocarcinoma in mice harboring a conditionally activatable allele of oncogenic K-ras. Here we show that the use of ...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Jackson EL,Willis N,Mercer K,Bronson RT,Crowley D,Montoya R,Jacks T,Tuveson DA

    更新日期:2001-12-15 00:00:00

  • Coregulation of anterior and posterior mesendodermal development by a hairy-related transcriptional repressor.

    abstract::During embryonic development in vertebrates, the endoderm becomes patterned along the anteroposterior axis to produce distinct derivatives. How this regulation is controlled is not well understood. We report that the zebrafish hairy/enhancer of split [E(spl)]-related gene her5 plays a critical role in this process. At...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Bally-Cuif L,Goutel C,Wassef M,Wurst W,Rosa F

    更新日期:2000-07-01 00:00:00

  • An intersubunit contact stimulating transcription initiation by E coli RNA polymerase: interaction of the alpha C-terminal domain and sigma region 4.

    abstract::The C-terminal domain of the Escherichia coli RNA polymerase (RNAP) alpha subunit (alphaCTD) stimulates transcription initiation by interacting with upstream (UP) element DNA and a variety of transcription activators. Here we identify specific substitutions in region 4.2 of sigma 70 (sigma(70)) and in alphaCTD that de...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Ross W,Schneider DA,Paul BJ,Mertens A,Gourse RL

    更新日期:2003-05-15 00:00:00

  • A PP2A regulatory subunit positively regulates Ras-mediated signaling during Caenorhabditis elegans vulval induction.

    abstract::We describe evidence that a regulatory B subunit of protein phosphatase 2A (PP2A) positively regulates an RTK-Ras-MAP kinase signaling cascade during Caenorhabditis elegans vulval induction. Although reduction of sur-6 PP2A-B function causes few vulval induction defects in an otherwise wild-type background, sur-6 PP2A...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Sieburth DS,Sundaram M,Howard RM,Han M

    更新日期:1999-10-01 00:00:00

  • Fission yeast genes that confer resistance to staurosporine encode an AP-1-like transcription factor and a protein kinase related to the mammalian ERK1/MAP2 and budding yeast FUS3 and KSS1 kinases.

    abstract::Staurosporine, a potent inhibitor of protein kinase C, arrests fission yeast cell elongation specifically at a stage immediately after cell division. We isolated two genes, which, when carried on multicopy plasmids, confer drug resistance in fission yeast. One, spk1+, encodes a protein kinase highly similar (54% ident...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Toda T,Shimanuki M,Yanagida M

    更新日期:1991-01-01 00:00:00

  • Normal human chromosomes have long G-rich telomeric overhangs at one end.

    abstract::Telomeres protect the ends of linear chromosomes from degradation and abnormal recombination events, and in vertebrates may be important in cellular senescence and cancer. However, very little is known about the structure of human telomeres. In this report we purify telomeres and analyze their termini. We show that fo...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Wright WE,Tesmer VM,Huffman KE,Levene SD,Shay JW

    更新日期:1997-11-01 00:00:00

  • Rad6 plays a role in transcriptional activation through ubiquitylation of histone H2B.

    abstract::Covalent modifications of the histone N tails play important roles in eukaryotic gene expression. Histone acetylation, in particular, is required for the activation of a subset of eukaryotic genes through the targeted recruitment of histone acetyltransferases. We have reported that a histone C tail modification, ubiqu...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Kao CF,Hillyer C,Tsukuda T,Henry K,Berger S,Osley MA

    更新日期:2004-01-15 00:00:00

  • A histone chaperone, DEK, transcriptionally coactivates a nuclear receptor.

    abstract::Chromatin reorganization is essential for transcriptional control by sequence-specific transcription factors. However, the molecular link between transcriptional control and chromatin reconfiguration remains unclear. By colocalization of the nuclear ecdysone receptor (EcR) on the ecdysone-induced puff in the salivary ...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Sawatsubashi S,Murata T,Lim J,Fujiki R,Ito S,Suzuki E,Tanabe M,Zhao Y,Kimura S,Fujiyama S,Ueda T,Umetsu D,Ito T,Takeyama K,Kato S

    更新日期:2010-01-15 00:00:00

  • A weak germ-line excision mutation blocks developmentally controlled amplification of the rDNA minichromosome of Tetrahymena thermophila.

    abstract::During development of the somatic macronucleus of Tetrahymena thermophila, the rDNA is excised from its germ-line chromosome, rearranged into a palindrome, and amplified to 10(4) copies. We have identified a cis-acting germ-line mutation, rmm11/6, that prevents amplification of the rDNA in all but approximately 1 in 1...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Kapler GM,Blackburn EH

    更新日期:1994-01-01 00:00:00

  • A genome-wide RNAi screen identifies multiple RSK-dependent regulators of cell migration.

    abstract::To define the functional pathways regulating epithelial cell migration, we performed a genome-wide RNAi screen using 55,000 pooled lentiviral shRNAs targeting ∼11,000 genes, selecting for transduced cells with increased motility. A stringent validation protocol generated a set of 31 genes representing diverse pathways...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Smolen GA,Zhang J,Zubrowski MJ,Edelman EJ,Luo B,Yu M,Ng LW,Scherber CM,Schott BJ,Ramaswamy S,Irimia D,Root DE,Haber DA

    更新日期:2010-12-01 00:00:00

  • mRNA 5'-leader trans-splicing in the chordates.

    abstract::We report the discovery of mRNA 5'-leader trans-splicing (SL trans-splicing) in the chordates. In the ascidian protochordate Ciona intestinalis, the mRNAs of at least seven genes undergo trans-splicing of a 16-nucleotide 5'-leader apparently derived from a 46-nucleotide RNA that shares features with previously charact...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Vandenberghe AE,Meedel TH,Hastings KE

    更新日期:2001-02-01 00:00:00

  • Sexual dimorphism in diverse metazoans is regulated by a novel class of intertwined zinc fingers.

    abstract::Sex determination is regulated by diverse pathways. Although upstream signals vary, a cysteine-rich DNA-binding domain (the DM motif) is conserved within downstream transcription factors of Drosophila melanogaster (Doublesex) and Caenorhabditis elegans (MAB-3). Vertebrate DM genes have likewise been identified and, re...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Zhu L,Wilken J,Phillips NB,Narendra U,Chan G,Stratton SM,Kent SB,Weiss MA

    更新日期:2000-07-15 00:00:00

  • Integrative genome analysis of somatic p53 mutant osteosarcomas identifies Ets2-dependent regulation of small nucleolar RNAs by mutant p53 protein.

    abstract::TP53 is the most frequently mutated gene in human cancer. Many mutant p53 proteins exert oncogenic gain-of-function (GOF) properties that contribute to metastasis, but the mechanisms mediating these functions remain poorly defined in vivo. To elucidate how mutant p53 GOF drives metastasis, we developed a traceable som...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Pourebrahim R,Zhang Y,Liu B,Gao R,Xiong S,Lin PP,McArthur MJ,Ostrowski MC,Lozano G

    更新日期:2017-09-15 00:00:00

  • A physiological role for gene loops in yeast.

    abstract::DNA loops that juxtapose the promoter and terminator regions of RNA polymerase II-transcribed genes have been identified in yeast and mammalian cells. Loop formation is transcription-dependent and requires components of the pre-mRNA 3'-end processing machinery. Here we report that looping at the yeast GAL10 gene persi...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Lainé JP,Singh BN,Krishnamurthy S,Hampsey M

    更新日期:2009-11-15 00:00:00

  • Evidence for a novel protease governing regulated intramembrane proteolysis and resistance to antimicrobial peptides in Bacillus subtilis.

    abstract::Evidence is presented that the activation of the RNA polymerase sigma factor sigma(W) in Bacillus subtilis by regulated intramembrane proteolysis is governed by a novel, membrane-embedded protease. The sigma(W) factor is activated by proteolytic destruction of the membrane-bound anti-sigma(W) factor RsiW in response t...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Ellermeier CD,Losick R

    更新日期:2006-07-15 00:00:00

  • The maternal sex determination gene daughterless has zygotic activity necessary for the formation of peripheral neurons in Drosophila.

    abstract::The daughterless (da) gene is known to have separate maternal and zygotic functions: Maternally supplied daughterless activity is required for proper sex determination and dosage compensation in female embryos, whereas loss of zygotically supplied da+ activity causes embryonic lethality in both male and female embryos...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Caudy M,Grell EH,Dambly-Chaudière C,Ghysen A,Jan LY,Jan YN

    更新日期:1988-07-01 00:00:00

  • The hematopoietic stem cell and its niche: a comparative view.

    abstract::Stem cells have been identified as a source of virtually all highly differentiated cells that are replenished during the lifetime of an animal. The critical balance between stem and differentiated cell populations is crucial for the long-term maintenance of functional tissue types. Stem cells maintain this balance by ...

    journal_title:Genes & development

    pub_type: 杂志文章,评审


    authors: Martinez-Agosto JA,Mikkola HK,Hartenstein V,Banerjee U

    更新日期:2007-12-01 00:00:00

  • Genome-wide analyses identify transcription factors required for proper morphogenesis of Drosophila sensory neuron dendrites.

    abstract::Dendrite arborization patterns are critical determinants of neuronal function. To explore the basis of transcriptional regulation in dendrite pattern formation, we used RNA interference (RNAi) to screen 730 transcriptional regulators and identified 78 genes involved in patterning the stereotyped dendritic arbors of cl...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Parrish JZ,Kim MD,Jan LY,Jan YN

    更新日期:2006-04-01 00:00:00

  • Loss of function of def selectively up-regulates Delta113p53 expression to arrest expansion growth of digestive organs in zebrafish.

    abstract::Transcription factor p53 forms a network with associated factors to regulate the cell cycle and apoptosis in response to environmental stresses. However, there is currently no direct genetic evidence to show if or how the p53 pathway functions during organogenesis. Here we present evidence to show that the zebrafish d...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Chen J,Ruan H,Ng SM,Gao C,Soo HM,Wu W,Zhang Z,Wen Z,Lane DP,Peng J

    更新日期:2005-12-01 00:00:00

  • Translational profiling of hypocretin neurons identifies candidate molecules for sleep regulation.

    abstract::Hypocretin (orexin; Hcrt)-containing neurons of the hypothalamus are essential for the normal regulation of sleep and wake behaviors and have been implicated in feeding, anxiety, depression, and reward. The absence of these neurons causes narcolepsy in humans and model organisms. However, little is known about the mol...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Dalal J,Roh JH,Maloney SE,Akuffo A,Shah S,Yuan H,Wamsley B,Jones WB,de Guzman Strong C,Gray PA,Holtzman DM,Heintz N,Dougherty JD

    更新日期:2013-03-01 00:00:00

  • A unique zinc finger protein is associated preferentially with active ecdysone-responsive loci in Drosophila.

    abstract::Using an immunochemical approach, we have identified a unique antigen, PEP (protein on ecdysone puffs), which is associated in third-instar larvae with the active ecdysone-regulated loci on polytene chromosomes; PEP is not associated with most intermolt puffs and is found on some, but not all, heat shock-induced puffs...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Amero SA,Elgin SC,Beyer AL

    更新日期:1991-02-01 00:00:00

  • Distinct molecular signals for nuclear import of the nucleolar snRNA, U3.

    abstract::Export to the cytoplasm of U3 RNA transcribed from a rat U3 gene injected into the nucleus of Xenopus oocytes indicates that the biogenesis of U3 RNA, like that of the previously studied Sm-precipitable nucleoplasmic snRNAs (U1, U2, U4, and U5), includes a cytoplasmic phase. The regulation of import of the U3 snRNA in...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Baserga SJ,Gilmore-Hebert M,Yang XW

    更新日期:1992-06-01 00:00:00

  • The RNA helicase MOV10L1 binds piRNA precursors to initiate piRNA processing.

    abstract::Piwi-piRNA (Piwi-interacting RNA) ribonucleoproteins (piRNPs) enforce retrotransposon silencing, a function critical for preserving the genome integrity of germ cells. The molecular functions of most of the factors that have been genetically implicated in primary piRNA biogenesis are still elusive. Here we show that M...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Vourekas A,Zheng K,Fu Q,Maragkakis M,Alexiou P,Ma J,Pillai RS,Mourelatos Z,Wang PJ

    更新日期:2015-03-15 00:00:00

  • Myxococcus CsgA, Drosophila Sniffer, and human HSD10 are cardiolipin phospholipases.

    abstract::Myxococcus xanthus development requires CsgA, a member of the short-chain alcohol dehydrogenase (SCAD) family of proteins. We show that CsgA and SocA, a protein that can replace CsgA function in vivo, oxidize the 2'-OH glycerol moiety on cardiolipin and phosphatidylglycerol to produce diacylglycerol (DAG), dihydroxyac...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Boynton TO,Shimkets LJ

    更新日期:2015-09-15 00:00:00

  • Anti-diabetic rosiglitazone remodels the adipocyte transcriptome by redistributing transcription to PPARγ-driven enhancers.

    abstract::Rosiglitazone (rosi) is a powerful insulin sensitizer, but serious toxicities have curtailed its widespread clinical use. Rosi functions as a high-affinity ligand for peroxisome proliferator-activated receptor γ (PPARγ), the adipocyte-predominant nuclear receptor (NR). The classic model, involving binding of ligand to...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Step SE,Lim HW,Marinis JM,Prokesch A,Steger DJ,You SH,Won KJ,Lazar MA

    更新日期:2014-05-01 00:00:00

  • Spatial arrangement of an RNA zipcode identifies mRNAs under post-transcriptional control.

    abstract::How RNA-binding proteins recognize specific sets of target mRNAs remains poorly understood because current approaches depend primarily on sequence information. In this study, we demonstrate that specific recognition of messenger RNAs (mRNAs) by RNA-binding proteins requires the correct spatial positioning of these seq...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Patel VL,Mitra S,Harris R,Buxbaum AR,Lionnet T,Brenowitz M,Girvin M,Levy M,Almo SC,Singer RH,Chao JA

    更新日期:2012-01-01 00:00:00

  • The an11 locus controlling flower pigmentation in petunia encodes a novel WD-repeat protein conserved in yeast, plants, and animals.

    abstract::In petunia flowers, the loci an1, an2, and an11 control the pigmentation of the flower by stimulating the transcription of anthocyanin biosynthetic genes. The an1 and an2 locus were recently cloned and encode a basic helix-loop-helix (bHLH) and MYB-domain transcriptional activator, respectively. Here, we report the is...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: de Vetten N,Quattrocchio F,Mol J,Koes R

    更新日期:1997-06-01 00:00:00

  • The regulation of empty spiracles by Abdominal-B mediates an abdominal segment identity function.

    abstract::The empty spiracles (ems) homeo box gene is required for the development of the Drosophila larval filzkörper, which are structural specializations of the eighth abdominal segment. Filzkörper development is also dependent on the function of the homeotic selector gene Abdominal-B (Abd-B). Here, we show that ems is a dow...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Jones B,McGinnis W

    更新日期:1993-02-01 00:00:00

  • Distinct requirements for Ras oncogenesis in human versus mouse cells.

    abstract::The spectrum of tumors associated with oncogenic Ras in humans often differs from those in mice either treated with carcinogens or engineered to sporadically express oncogenic Ras, suggesting that the mechanism of Ras transformation may be different in humans. Ras stimulates primarily three main classes of effector pr...

    journal_title:Genes & development

    pub_type: 杂志文章,评审


    authors: Hamad NM,Elconin JH,Karnoub AE,Bai W,Rich JN,Abraham RT,Der CJ,Counter CM

    更新日期:2002-08-15 00:00:00