Abstract：
:In response to DNA damage, cells activate a complex signal transduction network called the DNA damage response (DDR). To enhance our current understanding of the DDR network, we performed a genome-wide RNAi screen to identify genes required for resistance to ionizing radiation (IR). Along with a number of known DDR genes, we discovered a large set of novel genes whose depletion leads to cellular sensitivity to IR. Here we describe TTI1 (Tel two-interacting protein 1) and TTI2 as highly conserved regulators of the DDR in mammals. TTI1 and TTI2 protect cells from spontaneous DNA damage, and are required for the establishment of the intra-S and G2/M checkpoints. TTI1 and TTI2 exist in multiple complexes, including a 2-MDa complex with TEL2 (telomere maintenance 2), called the Triple T complex, and phosphoinositide-3-kinase-related protein kinases (PIKKs) such as ataxia telangiectasia-mutated (ATM). The components of the TTT complex are mutually dependent on each other, and act as critical regulators of PIKK abundance and checkpoint signaling.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Hurov KE,Cotta-Ramusino C,Elledge SJdoi
10.1101/gad.1934210subject
Has Abstractpub_date
2010-09-01 00:00:00pages
1939-50issue
17eissn
0890-9369issn
1549-5477pii
24/17/1939journal_volume
24pub_type
杂志文章abstract：:Oligophrenin-1 (OPHN1) encodes a Rho-GTPase-activating protein (Rho-GAP) whose loss of function has been associated with X-linked mental retardation (MR). The pathophysiological role of OPHN1, however, remains poorly understood. Here we show that OPHN1 through its Rho-GAP activity plays a critical role in the activity...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.1783809
更新日期：2009-06-01 00:00:00
abstract：:eIF2B is a heteropentameric guanine-nucleotide exchange factor essential for protein synthesis initiation in eukaryotes. Its activity is inhibited in response to starvation or stress by phosphorylation of the alpha subunit of its substrate, translation initiation factor eIF2, resulting in reduced rates of translation ...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.12.4.514
更新日期：1998-02-15 00:00:00
abstract：:While microRNAs (miRNAs) regulate the vast majority of protein-encoding transcripts, little is known about how miRNAs themselves are degraded. We recently described Tudor-staphylococcal/micrococcal-like nuclease (TSN)-mediated miRNA decay (TumiD) as a cellular pathway in which the nuclease TSN promotes the decay of mi...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.303537.117
更新日期：2017-07-15 00:00:00
abstract：:Restricted expression of a mouse Vasa homolog gene (Mvh) expression is first detected in primordial germ cells (PGCs) after colonization of the genital ridges. Subsequently, Mvh is maintained until postmeiotic germ cells are formed. Here, we demonstrate that male mice homozygous for a targeted mutation of Mvh exhibit ...
journal_title：Genes & development
pub_type： 杂志文章
doi：
更新日期：2000-04-01 00:00:00
abstract：:Exposure of hematopoietic progenitors to gamma-irradiation (IR) induces p53-dependent apoptosis and a p53-independent G2/M cell cycle arrest. These responses to DNA-damage can be inhibited by treatment with cytokine growth factors. Here we report that gamma-IR-induced apoptosis and cell cycle arrest are suppressed by ...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.12.8.1099
更新日期：1998-04-15 00:00:00
abstract：:Glucocorticoid (GC) receptor (GR) has been shown recently to bind a subset of mRNAs and elicit rapid mRNA degradation. However, the molecular details of GR-mediated mRNA decay (GMD) remain unclear. Here, we demonstrate that GMD triggers rapid degradation of target mRNAs in a translation-independent and exon junction c...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.286484.116
更新日期：2016-09-15 00:00:00
abstract：:In somatic cells of Xenopus, transcription of the TFIIIA gene initiates greater than 200 bp upstream from the start site used in oocytes. The resultant mRNA encodes a protein, S-TFIIIA, that is 22 amino acids longer at its amino terminus than the abundant form of TFIIIA in oocytes (O-TFIIIA). S-TFIIIA binds the 5S RNA...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.4.9.1602
更新日期：1990-09-01 00:00:00
abstract：:To investigate the relationship between splicing and polyadenylation during the production of vertebrate mRNAs, we examined the effect of mutation of a poly(A) site on splicing of upstream introns. Mutation of the AAUAAA polyadenylation consensus sequence inhibited in vitro splicing of an upstream intron. The magnitud...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.5.11.2086
更新日期：1991-11-01 00:00:00
abstract：:Two retrovirus promoter trap vectors (U3His and U3Neo) have been used to disrupt genes expressed in totipotent murine embryonal stem (ES) cells. Selection in L-histidinol or G418 produced clones in which the coding sequences for histidinol-dehydrogenase or neomycin-phosphotransferase were fused to sequences in or near...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.6.6.919
更新日期：1992-06-01 00:00:00
abstract：:Many small nucleolar RNAs (snoRNAs) in vertebrates are encoded within introns of protein genes. We have reported previously that two isoforms of human U17 snoRNA are encoded in introns of the cell-cycle regulatory gene, RCC1. We have now investigated the mechanism of processing of U17 RNAs and of another intron-encode...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.9.11.1411
更新日期：1995-06-01 00:00:00
abstract：:We have shown that Wnt signals are necessary and sufficient for neural crest cells to adopt pigment cell fates. nacre, a zebrafish homolog of MITF, is required for pigment cell differentiation. We isolated a promoter region of nacre that contains Tcf/Lef binding sites, which can mediate Wnt responsiveness. This promot...
journal_title：Genes & development
pub_type： 杂志文章
doi：
更新日期：2000-01-15 00:00:00
abstract：:During gastrulation of Xenopus embryos the prospective mesoderm is induced initially with domains of dorsal and ventral fate, then further patterned to generate somitic mesoderm by signals from the gastrula organizer. Although Xwnt-8 is expressed in future ventrolateral mesoderm and induces prospective epidermis to di...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.10.21.2805
更新日期：1996-11-01 00:00:00
abstract：:The myogenic regulatory factor MyoD dimerizes with other positive and negative regulatory factors through a conserved region called the helix-loop-helix (HLH) domain. Using a non-DNA-binding MyoD mutant with a normal HLH domain as a dimerization competitor in gel mobility shift assays in conjunction with various MyoD ...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.7.12a.2456
更新日期：1993-12-01 00:00:00
abstract：:Post-translational modifications of conserved N-terminal tail residues in histones regulate many aspects of chromosome activity. Thr 3 of histone H3 is highly conserved, but the significance of its phosphorylation is unclear, and the identity of the corresponding kinase unknown. Immunostaining with phospho-specific an...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.1267105
更新日期：2005-02-15 00:00:00
abstract：:The Hox-2 locus on chromosome 11 represents one of the major clusters of homeo-box-containing genes in the mouse. We have identified two new members (Hox-2.6 and Hox-2.7), which form part of this cluster of seven linked genes, and it appears that the Hox-2 locus is related by duplication and divergence to at least one...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.2.11.1424
更新日期：1988-11-01 00:00:00
abstract：:Glucose and glutamine serve as the two primary carbon sources in proliferating cells, and uptake of both nutrients is directed by growth factor signaling. Although either glucose or glutamine can potentially support mitochondrial tricarboxylic acid (TCA) cycle integrity and ATP production, we found that glucose depriv...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.1985910
更新日期：2010-12-15 00:00:00
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
doi：10.1101/gad.1553007
更新日期：2007-08-01 00:00:00
abstract：:Coliphage N4 is a double-stranded DNA virus that requires the sequential activity of three different RNA polymerases during infection. The N4 virion RNA polymerase, which is carried in the virion and is injected with the DNA at the start of infection, is responsible for the synthesis of N4 early RNAs. In vitro, the vi...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.6.10.2010
更新日期：1992-10-01 00:00:00
abstract：:Chromosomal translocations are a hallmark of hematopoietic malignancies. The initial molecular events or pathways that lead to translocations in hematopoietic cells are largely unknown, particularly in the stem cell-enriched population postulated to be the initial target for these events. We used in vitro differentiat...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.1522807
更新日期：2007-05-01 00:00:00
abstract：:Nonhomologous end joining (NHEJ) and homologous recombination (HR) represent the two major pathways of DNA double-strand break (DSB) repair in eukaryotic cells. NHEJ repairs DSBs by ligation of cognate broken ends irrespective of homologous flanking sequences, whereas HR repairs DSBs using an undamaged homologous temp...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.1204304
更新日期：2004-06-01 00:00:00
abstract：:Irradiation in the G1 phase of the cell cycle delays the onset of DNA synthesis and transiently inhibits the activation of replication origins in mammalian cells. It has been suggested that this inhibition is the result of the loss of torsional tension in the DNA after it has been damaged. Because irradiation causes D...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.8.5.554
更新日期：1994-03-01 00:00:00
abstract：:Expression of the gene encoding atrial natriuretic factor (ANF) during mouse cardiac embryogenesis was studied using in situ hybridization to histologic sections. ANF mRNA was first detected in a subpopulation of myocardial cells at day 8 of embryogenesis. During day 9, abundant hybridization of the ANF probe to the a...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.1.7.693
更新日期：1987-09-01 00:00:00
abstract：:The enzyme telomerase, which elongates chromosome termini, is a critical factor in determining long-term cellular proliferation and tissue renewal. Hence, even small differences in telomerase levels can have substantial consequences for human health. In budding yeast, telomerase consists of the catalytic Est2 protein ...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.246256.114
更新日期：2014-10-01 00:00:00
abstract：:The RNA polymerase II (RNAPII) C-terminal domain kinase, CDK12, regulates genome stability, expression of DNA repair genes, and cancer cell resistance to chemotherapy and immunotherapy. In addition to its role in mRNA biosynthesis of DNA repair genes, we show here that CDK12 phosphorylates the mRNA 5' cap-binding repr...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.322339.118
更新日期：2019-04-01 00:00:00
abstract：:Mitotic duration is determined by activation of the anaphase-promoting complex/cyclosome (APC/C) bound to its coactivator, Cdc20. Kinetochores, the microtubule-interacting machines on chromosomes, restrain mitotic exit when not attached to spindle microtubules by generating a Cdc20-containing complex that inhibits the...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.302067.117
更新日期：2017-06-01 00:00:00
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
doi：10.1101/gad.212738.112
更新日期：2013-03-15 00:00:00
abstract：:In many eukaryotes, siRNAs bound to Argonaute proteins guide chromatin-modifying enzymes to complementary loci, resulting in transcriptional gene silencing. Multiple lines of evidence indicate that siRNAs base-pair with longer RNAs produced at target loci, but the possibility that siRNAs base-pair directly with DNA re...
journal_title：Genes & development
pub_type： 评论,杂志文章
doi：10.1101/gad.294900.116
更新日期：2016-12-15 00:00:00
abstract：:Heparan sulfate proteoglycans have been implicated in the presentation of a number of secreted signaling molecules to their signal-transducing receptors. We have characterized a gene trap mutation in the gene encoding a heparan sulfate biosynthetic enzyme, heparan sulfate 2-sulfotransferase (HS2ST). Transgenic mice we...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.12.12.1894
更新日期：1998-06-15 00:00:00
abstract：:Histone deacetylase 3 (HDAC3) is one of four members of the human class I HDACs that regulates gene expression by deacetylation of histones and nonhistone proteins. Early studies have suggested that HDAC3 activity is regulated by association with the corepressors N-CoR and SMRT. Here we demonstrate that, in addition t...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.1286005
更新日期：2005-04-01 00:00:00
abstract：:RUNX1/AML1 is required for the development of definitive hematopoiesis, and its activity is altered by mutations, deletions, and chromosome translocations in human acute leukemia. RUNX1 function can be regulated by post-translational modifications and protein-protein interactions. We show that RUNX1 is arginine-methyl...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.1632608
更新日期：2008-03-01 00:00:00
