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














  • An adenovirus early region 4 gene product is required for induction of the infection-specific form of cellular E2F activity.

    abstract::E2F is a cellular, sequence-specific DNA-binding factor that binds to pairs of sites that occur upstream of the E1A and E2 early mRNA cap sites. During adenovirus infection, there is induction of a form of E2F that binds cooperatively to the pair of sites in the E2 control region. Production of the infection-specific ...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Hardy S,Engel DA,Shenk T

    更新日期:1989-07-01 00:00:00

  • Intronic sequence elements impede exon ligation and trigger a discard pathway that yields functional telomerase RNA in fission yeast.

    abstract::The fission yeast telomerase RNA (TER1) precursor harbors an intron immediately downstream from its mature 3' end. Unlike most introns, which are removed from precursor RNAs by the spliceosome in two sequential but tightly coupled transesterification reactions, TER1 only undergoes the first cleavage reaction during te...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Kannan R,Hartnett S,Voelker RB,Berglund JA,Staley JP,Baumann P

    更新日期:2013-03-15 00:00:00

  • The role of a Williams-Beuren syndrome-associated helix-loop-helix domain-containing transcription factor in activin/nodal signaling.

    abstract::We investigated the regulation of the activin/nodal-inducible distal element (DE) of the Xenopus goosecoid (gsc) promoter. On the basis of its interaction with the DE, we isolated a Xenopus homolog of the human Williams-Beuren syndrome critical region 11 (XWBSCR11), and further, show that it interacts with pathway-spe...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Ring C,Ogata S,Meek L,Song J,Ohta T,Miyazono K,Cho KW

    更新日期:2002-04-01 00:00:00

  • Deficient mismatch repair improves organismal fitness and survival of mice with dysfunctional telomeres.

    abstract::Mismatch repair (MMR) has important roles in meiotic and mitotic recombination, DNA damage signaling, and various aspects of DNA metabolism including class-switch recombination, somatic hypermutation, and triplet-repeat expansion. Defects in MMR are responsible for human cancers characterized by microsatellite instabi...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Siegl-Cachedenier I,Muñoz P,Flores JM,Klatt P,Blasco MA

    更新日期:2007-09-01 00:00:00

  • Heartless, a Drosophila FGF receptor homolog, is essential for cell migration and establishment of several mesodermal lineages.

    abstract::A Drosophila FGF receptor homolog (DFGF-R2/DFRI) termed Heartless (Htl) is expressed in the embryonic mesoderm. The phenotypes of null mutant embryos demonstrated that Htl is a central player that is required for the development of several mesodermal lineages. No abnormalities in the primary specification of the mesod...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Beiman M,Shilo BZ,Volk T

    更新日期:1996-12-01 00:00:00

  • A specific protein substrate for a deubiquitinating enzyme: Liquid facets is the substrate of Fat facets.

    abstract::Eukaryotic genomes encode large families of deubiquitinating enzymes (DUBs). Genetic data suggest that Fat facets (Faf), a Drosophila DUB essential for patterning the compound eye, might have a novel regulatory function; Faf might reverse the ubiquitination of a specific substrate, thereby preventing proteasomal degra...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Chen X,Zhang B,Fischer JA

    更新日期:2002-02-01 00:00:00

  • Seven-up, the Drosophila homolog of the COUP-TF orphan receptors, controls cell proliferation in the insect kidney.

    abstract::Morphogenesis of the insect kidney, the Malpighian tubules, is controlled in Drosophila by a single large cell, the tip cell. It has been postulated that this cell sends out a mitogenic signal that induces the division of neighboring cells. The signal and the molecules that receive it have remained elusive. We show th...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Kerber B,Fellert S,Hoch M

    更新日期:1998-06-15 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

  • Ssn6-Tup1 interacts with class I histone deacetylases required for repression.

    abstract::Ssn6-Tup1 regulates multiple genes in yeast, providing a paradigm for corepressor functions. Tup1 interacts directly with histones H3 and H4, and mutation of these histones synergistically compromises Ssn6-Tup1-mediated repression. In vitro, Tup1 interacts preferentially with underacetylated isoforms of H3 and H4, sug...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Watson AD,Edmondson DG,Bone JR,Mukai Y,Yu Y,Du W,Stillman DJ,Roth SY

    更新日期:2000-11-01 00:00:00

  • p62/SQSTM1 synergizes with autophagy for tumor growth in vivo.

    abstract::Autophagy is crucial for cellular homeostasis and plays important roles in tumorigenesis. FIP200 (FAK family-interacting protein of 200 kDa) is an essential autophagy gene required for autophagy induction, functioning in the ULK1-ATG13-FIP200 complex. Our previous studies showed that conditional knockout of FIP200 sig...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Wei H,Wang C,Croce CM,Guan JL

    更新日期:2014-06-01 00:00:00

  • BR-dependent phosphorylation modulates PIF4 transcriptional activity and shapes diurnal hypocotyl growth.

    abstract::Signaling by the hormones brassinosteroid (BR) and gibberellin (GA) is critical to normal plant growth and development and is required for hypocotyl elongation in response to dark and elevated temperatures. Active BR signaling is essential for GA promotion of hypocotyl growth and suppresses the dwarf phenotype of GA m...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Bernardo-García S,de Lucas M,Martínez C,Espinosa-Ruiz A,Davière JM,Prat S

    更新日期:2014-08-01 00:00:00

  • Sarkosyl defines three intermediate steps in transcription initiation by RNA polymerase III: application to stimulation of transcription by E1A.

    abstract::We used Sarkosyl to analyze steps along the pathway of transcription initiation by RNA polymerase III. Sarkosyl (0.015%) inhibited transcription when present prior to incubation of RNA polymerase III, TFIIIB, and TFIIIC with the VAI gene, whereas it had no detectable effect on initiation or reinitiation of transcripti...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Kovelman R,Roeder RG

    更新日期:1990-04-01 00:00:00

  • Selection of the initiator tRNA by Escherichia coli initiation factors.

    abstract::We have developed a new technique, called 'toeprinting,' which has allowed a study of the tRNA-binding properties of Escherichia coli translation initiation complexes. In response to natural mRNAs, the initiator tRNA and a variety of elongator tRNAs bind to the same tRNA-binding site on the 30S ribosomal subunit as lo...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Hartz D,McPheeters DS,Gold L

    更新日期:1989-12-01 00:00:00

  • The cyclic gene Hes1 contributes to diverse differentiation responses of embryonic stem cells.

    abstract::Stem cells do not all respond the same way, but the mechanisms underlying this heterogeneity are not well understood. Here, we found that expression of Hes1 and its downstream genes oscillate in mouse embryonic stem (ES) cells. Those expressing low and high levels of Hes1 tended to differentiate into neural and mesode...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Kobayashi T,Mizuno H,Imayoshi I,Furusawa C,Shirahige K,Kageyama R

    更新日期:2009-08-15 00:00:00

  • Terminal differentiation of myelin-forming oligodendrocytes depends on the transcription factor Sox10.

    abstract::Sox10 is a high-mobility-group transcriptional regulator in early neural crest. Without Sox10, no glia develop throughout the peripheral nervous system. Here we show that Sox10 is restricted in the central nervous system to myelin-forming oligodendroglia. In Sox10-deficient mice progenitors develop, but terminal diffe...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Stolt CC,Rehberg S,Ader M,Lommes P,Riethmacher D,Schachner M,Bartsch U,Wegner M

    更新日期:2002-01-15 00:00:00

  • Four histone variants mark the boundaries of polycistronic transcription units in Trypanosoma brucei.

    abstract::Unusually for a eukaryote, genes transcribed by RNA polymerase II (pol II) in Trypanosoma brucei are arranged in polycistronic transcription units. With one exception, no pol II promoter motifs have been identified, and how transcription is initiated remains an enigma. T. brucei has four histone variants: H2AZ, H2BV, ...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Siegel TN,Hekstra DR,Kemp LE,Figueiredo LM,Lowell JE,Fenyo D,Wang X,Dewell S,Cross GA

    更新日期:2009-05-01 00:00:00

  • So many pieces, one puzzle: cell type specification and visual circuitry in flies and mice.

    abstract::The visual system is a powerful model for probing the development, connectivity, and function of neural circuits. Two genetically tractable species, mice and flies, are together providing a great deal of understanding of these processes. Current efforts focus on integrating knowledge gained from three cross-fostering ...

    journal_title:Genes & development

    pub_type: 杂志文章,评审


    authors: Wernet MF,Huberman AD,Desplan C

    更新日期:2014-12-01 00:00:00

  • Breaking down bone: new insight into site-specific mechanisms of breast cancer osteolysis mediated by metalloproteinases.

    abstract::Bone metastases are the most common skeletal complication of malignancy. Tumor cells disrupt normal bone remodeling to promote bone destruction and its associated morbidity. In the August 15, 2009, issue of Genes & Development, Lu and colleagues (pp. 1882-1894) propose a novel molecular mechanism by which tumor-produc...

    journal_title:Genes & development

    pub_type: 评论,杂志文章


    authors: Guise TA

    更新日期:2009-09-15 00:00:00

  • Nascent-seq indicates widespread cotranscriptional pre-mRNA splicing in Drosophila.

    abstract::To determine the prevalence of cotranscriptional splicing in Drosophila, we sequenced nascent RNA transcripts from Drosophila S2 cells as well as from Drosophila heads. Eighty-seven percent of the introns assayed manifest >50% cotranscriptional splicing. The remaining 13% are cotranscriptionally spliced poorly or slow...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Khodor YL,Rodriguez J,Abruzzi KC,Tang CH,Marr MT 2nd,Rosbash M

    更新日期:2011-12-01 00:00:00

  • Cdc34 and the F-box protein Met30 are required for degradation of the Cdk-inhibitory kinase Swe1.

    abstract::Ubiquitin-mediated proteolysis controls the abundance of many cell cycle regulatory proteins. Recent work in Saccharomyces cerevisiae suggests that a complex consisting of Cdc53, Skp1, and a third component known as an F-box protein (termed SCF) in combination with Cdc34 specifically targets regulatory proteins for de...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Kaiser P,Sia RA,Bardes EG,Lew DJ,Reed SI

    更新日期:1998-08-15 00:00:00

  • The nucleotides responsible for the direct physical contact between the chromatin insulator protein CTCF and the H19 imprinting control region manifest parent of origin-specific long-distance insulation and methylation-free domains.

    abstract::The repression of the maternally inherited Igf2 allele has been proposed to depend on a methylation-sensitive chromatin insulator organized by the 11 zinc finger protein CTCF at the H19 imprinting control region (ICR). Here we document that point mutations of the nucleotides in physical contact with CTCF within the en...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Pant V,Mariano P,Kanduri C,Mattsson A,Lobanenkov V,Heuchel R,Ohlsson R

    更新日期:2003-03-01 00:00:00

  • Transcription factor CREM coordinates the timing of hepatocyte proliferation in the regenerating liver.

    abstract::The liver regenerates upon partial hepatectomy (PH) as terminally differentiated hepatocytes undergo a tremendous proliferative process. CREM gene expression is powerfully induced during liver regeneration. We show that cell proliferation is significantly reduced upon PH in CREM-/- mice. There is a reduction in DNA sy...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Servillo G,Della Fazia MA,Sassone-Corsi P

    更新日期:1998-12-01 00:00:00

  • Nuclear receptor ERR alpha and coactivator PGC-1 beta are effectors of IFN-gamma-induced host defense.

    abstract::Macrophage activation by the proinflammatory cytokine interferon-gamma (IFN-gamma) is a critical component of the host innate response to bacterial pathogenesis. However, the precise nature of the IFN-gamma-induced activation pathway is not known. Here we show using genome-wide expression and chromatin-binding profili...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Sonoda J,Laganière J,Mehl IR,Barish GD,Chong LW,Li X,Scheffler IE,Mock DC,Bataille AR,Robert F,Lee CH,Giguère V,Evans RM

    更新日期:2007-08-01 00:00:00

  • Cell fusion induced by ERVWE1 or measles virus causes cellular senescence.

    abstract::Cellular senescence limits proliferation of potentially detrimental cells, preventing tumorigenesis and restricting tissue damage. However, the function of senescence in nonpathological conditions is unknown. We found that the human placental syncytiotrophoblast exhibited the phenotype and expressed molecular markers ...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Chuprin A,Gal H,Biron-Shental T,Biran A,Amiel A,Rozenblatt S,Krizhanovsky V

    更新日期:2013-11-01 00:00:00

  • Cap-independent translation of encephalomyocarditis virus RNA: structural elements of the internal ribosomal entry site and involvement of a cellular 57-kD RNA-binding protein.

    abstract::Translation of encephalomyocarditis virus (EMCV) mRNA occurs by ribosomal internal entry into the 5'-nontranslated region (5' NTR) rather than by ribosomal scanning. The internal ribosomal entry site (IRES) in the EMCV 5' NTR was determined by in vitro translation with RNAs that were generated by in vitro transcriptio...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Jang SK,Wimmer E

    更新日期:1990-09-01 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

  • Genetics and biology of pancreatic ductal adenocarcinoma.

    abstract::Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death in the United States with a median survival of <6 mo and a dismal 5-yr survival rate of 3%-5%. The cancer's lethal nature stems from its propensity to rapidly disseminate to the lymphatic system and distant organs. This aggressive biol...

    journal_title:Genes & development

    pub_type: 杂志文章,评审


    authors: Hezel AF,Kimmelman AC,Stanger BZ,Bardeesy N,Depinho RA

    更新日期:2006-05-15 00:00:00

  • The HIV-1 Tat protein activates transcription from an upstream DNA-binding site: implications for Tat function.

    abstract::The Tat protein of human immunodeficiency virus type 1 (HIV-1) activates transcription following binding to nascent trans-activation response (TAR) RNA downstream of the transcription start site. Because Tat functions when bound to RNA, and in a position-dependent manner, it has been proposed that Tat works by a novel...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Southgate CD,Green MR

    更新日期:1991-12-01 00:00:00

  • Role of the rasGAP-associated docking protein p62(dok) in negative regulation of B cell receptor-mediated signaling.

    abstract::Antigenic stimulation of the B-cell receptor (BCR) is a central event in the immune response. In contrast, antigen bound to IgG negatively regulates signals from the BCR by cross-linking it to the inhibitory receptor FcgammaRIIB. Here we show that upon cross-linking of BCR or BCR with FcgammaRIIB, the rasGAP-associate...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Yamanashi Y,Tamura T,Kanamori T,Yamane H,Nariuchi H,Yamamoto T,Baltimore D

    更新日期:2000-01-01 00:00:00

  • A condensin-like dosage compensation complex acts at a distance to control expression throughout the genome.

    abstract::In many species, a dosage compensation complex (DCC) is targeted to X chromosomes of one sex to equalize levels of X-gene products between males (1X) and females (2X). Here we identify cis-acting regulatory elements that target the Caenorhabditis elegans X chromosome for repression by the DCC. The DCC binds to discret...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Jans J,Gladden JM,Ralston EJ,Pickle CS,Michel AH,Pferdehirt RR,Eisen MB,Meyer BJ

    更新日期:2009-03-01 00:00:00