Abstract：
:Genetic and cytologic data from Saccharomyces cerevisiae and mammals implicate the Mre11 complex, consisting of Mre11, Rad50, and Nbs1, as a sensor of DNA damage, and indicate that the complex influences the activity of ataxia-telangiectasia mutated (ATM) in the DNA damage response. Rad50(S/S) mice exhibit precipitous apoptotic attrition of hematopoietic cells. We generated ATM- and Chk2-deficient Rad50(S/S) mice and found that Rad50(S/S) cellular attrition was strongly ATM and Chk2 dependent. The hypomorphic Mre11(ATLD1) and Nbs1(Delta)(B) alleles conferred similar rescue of Rad50(S/S)-dependent hematopoietic failure. These data indicate that the Mre11 complex activates an ATM-Chk2-dependent apoptotic pathway. We find that apoptosis and cell cycle checkpoint activation are parallel outcomes of the Mre11 complex-ATM pathway. Conversely, the Rad50(S) mutation mitigated several phenotypic features of ATM deficiency. We propose that the Rad50(S) allele is hypermorphic for DNA damage signaling, and that the resulting constitutive low-level activation of the DNA damage response accounts for the partial suppression of ATM deficiency in Rad50(S/S) Atm(-/-) mice.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Morales M,Theunissen JW,Kim CF,Kitagawa R,Kastan MB,Petrini JHdoi
10.1101/gad.1373705subject
Has Abstractpub_date
2005-12-15 00:00:00pages
3043-54issue
24eissn
0890-9369issn
1549-5477pii
19/24/3043journal_volume
19pub_type
杂志文章abstract：:Telomerase is a ribonucleoprotein enzyme that adds telomeric repeats to chromosomes, maintaining telomere length and stabilizing chromosome ends. In vitro, telomerase from the ciliate Tetrahymena elongates single-stranded, guanosine-rich DNA primers by adding repeats of the Tetrahymena telomeric sequence, dT2G4. We ha...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.7.7b.1364
更新日期：1993-07-01 00:00:00
abstract：:Directed cell motility is at the basis of biological phenomena such as development, wound healing, and metastasis. It has been shown that substrate attachments mediate motility by coupling the cell's cytoskeleton with force generation. However, it has been unclear how the persistence of cell directionality is facilita...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.190413.112
更新日期：2012-09-01 00:00:00
abstract：:Lipids play crucial roles in many aspects of glial cell biology, affecting processes ranging from myelin membrane biosynthesis to axo-glial interactions. In order to study the role of lipid metabolism in myelinating glial cells, we specifically deleted in Schwann cells the Lpin1 gene, which encodes the Mg2+-dependent ...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.1638008
更新日期：2008-06-15 00:00:00
abstract：:Cell fates in the optic neuroepithelium are determined by the combinational action of homeotic transcription factors. One of these is Vax2, a homeodomain protein that ventralizes the vertebrate eye field by repressing transcription of the Pax6 gene. We find that Vax2 shuttles between the nucleus and cytoplasm as a fun...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.1462706
更新日期：2006-10-15 00:00:00
abstract：:The human T cell-specific transcription factor TCF-1 alpha plays a key role in the tissue-specific activation of the T cell receptor (TCR) C alpha enhancer and binds to pyrimidine-rich elements (5'-PyCTTTG-3') present in a variety of other T cell-specific control regions. Using amino acid sequence information derived ...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.5.4.656
更新日期：1991-04-01 00:00:00
abstract：:The recombination site dif is the target on the Escherichia coli chromosome of the site-specific recombinases XerC and XerD. The dif/XerC-D system plays a role during the cell cycle, probably by favoring sister chromosome monomerization or separation. A phenomenon of regional control over dif activity, also analyzed i...
journal_title：Genes & development
pub_type： 评论,杂志文章
doi：10.1101/gad.10.9.1152
更新日期：1996-05-01 00:00:00
abstract：:In enteric bacteria, the transcription factor σ(E) maintains membrane homeostasis by inducing synthesis of proteins involved in membrane repair and two small regulatory RNAs (sRNAs) that down-regulate synthesis of abundant membrane porins. Here, we describe the discovery of a third σ(E)-dependent sRNA, MicL (mRNA-inte...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.243485.114
更新日期：2014-07-15 00:00:00
abstract：:Several previously known transcription cofactors have been demonstrated in vitro recently to be histone acetyltransferases and deacetyltransferases, suggesting that remodeling of chromatin through histone acetylation plays a fundamental role in gene regulation. Clear evidence has not yet been obtained, however, to dem...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.12.5.640
更新日期：1998-03-01 00:00:00
abstract：:Pcf11 is one of numerous proteins involved in pre-mRNA 3'-end processing and transcription termination. Using elongation complexes (ECs) formed from purified yeast RNA polymerase II (Pol II), we show that a 140-amino acid polypeptide from yeast Pcf11 is capable of dismantling the EC in vitro. This action depends on th...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.1296305
更新日期：2005-07-01 00:00:00
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journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.1439206
更新日期：2006-09-15 00:00:00
abstract：:An insulin receptor-like signaling pathway regulates Caenorhabditis elegans metabolism, development, and longevity. Inactivation of the insulin receptor homolog DAF-2, the AGE-1 PI3K, or the AKT-1 and AKT-2 kinases causes a developmental arrest at the dauer stage. A null mutation in the daf-16 Fork head transcription ...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.13.11.1438
更新日期：1999-06-01 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：:Most eukaryotic mRNAs are translated using a cap-dependent mechanism of translation. However, approximately 10% of mammalian mRNAs initiate translation using a cap-independent mechanism that is not well understood. These mRNAs contain an internal ribosome entry site (IRES) located in the 5' untranslated region. The cr...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.1832209
更新日期：2009-12-01 00:00:00
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
doi：10.1101/gad.829100
更新日期：2000-11-01 00:00:00
abstract：:We describe the developmental effects of the expression of a normal and mutated Drosophila ras gene ras2 in transgenic Drosophila. A Gly14----Val14 mutant (Gly14 in ras2 is equivalent to Gly12 in mammalian ras proteins) was constructed in ras2 by site-directed mutagenesis. Inducible constructs of ras2 and ras2Val14 we...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.2.5.567
更新日期：1988-05-01 00:00:00
abstract：:The homeless (hls) gene of Drosophila is required for anteroposterior and dorsoventral axis formation during oogenesis. At a low frequency, females homozygous for mutations in hls generate early egg chambers in which the oocyte is positioned incorrectly within the cyst. At a high frequency, late-stage egg chambers exh...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.9.20.2495
更新日期：1995-10-15 00:00:00
abstract：:To find new genes that influence liver lipid mass, we performed a genetic screen for zebrafish mutants with hepatic steatosis, a pathological accumulation of fat. The red moon (rmn) mutant develops hepatic steatosis as maternally deposited yolk is depleted. Conversely, hepatic steatosis is suppressed in rmn mutants by...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.180968.111
更新日期：2012-02-01 00:00:00
abstract：:The mitotic kinase Aurora A (Aur-A) is required for formation of a bipolar mitotic spindle and accurate chromosome segregation. In somatic cells, Aur-A protein and kinase activity levels peak during mitosis, and Aur-A is degraded during mitotic exit. Here, we investigated how Aur-A protein and kinase activity levels a...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.1007302
更新日期：2002-09-01 00:00:00
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
doi：10.1101/gad.1366405
更新日期：2005-12-01 00:00:00
abstract：:Upon activation by far-red light, phytochrome A signals are transduced through several pathways to promote photomorphogenesis. The COP1 E3 ligase represses photomorphogenesis in part by targeting transcription activators such as LAF1 and HY5 for destruction. Another positive regulator of photomorphogenesis is HFR1, a ...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.1247205
更新日期：2005-03-01 00:00:00
abstract：:The cytochrome P450 (CYP) gene products such as CYP3A and CYP2B are essential for the metabolism of steroid hormones and xenochemicals including prescription drugs. Nuclear receptor SXR/PXR (steroid and xenobiotic receptor/pregnenolone X receptor) has been shown both biochemically and genetically to activate CYP3A gen...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.846800
更新日期：2000-12-01 00:00:00
abstract：:Telomere proteins protect the chromosomal terminus from nucleolytic degradation and end-to-end fusion, and they may contribute to telomere length control and the regulation of telomerase. The current studies investigate the effect of Oxytricha single-stranded telomere DNA-binding protein subunits alpha and beta on tel...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.12.10.1504
更新日期：1998-05-15 00:00:00
abstract：:The female mammary gland is a very dynamic organ that undergoes continuous tissue remodeling during adulthood. Although it is well established that the number of menstrual cycles and pregnancy (in this case transiently) increase the risk of breast cancer, the reasons are unclear. Growing clinical and experimental evid...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.292318.116
更新日期：2017-03-15 00:00:00
abstract：:The transcription factor Ebf1 is an important determinant of early B lymphopoiesis. To gain insight into the functions of Ebf1 at distinct stages of differentiation, we conditionally inactivated Ebf1. We found that Ebf1 is required for the proliferation, survival, and signaling of pro-B cells and peripheral B-cell sub...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.187328.112
更新日期：2012-04-01 00:00:00
abstract：:Drosophila melanogaster neural-specific protein, ELAV, has been shown to regulate the neural-specific splicing of three genes: neuroglian (nrg), erect wing, and armadillo. Alternative splicing of the nrg transcript involves alternative inclusion of a 3'-terminal exon. Here, using a minigene reporter, we show that the ...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.903101
更新日期：2001-10-01 00:00:00
abstract：:The nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ) is known to regulate lipid metabolism in many tissues, including macrophages. Here we report that peritoneal macrophage respiration is enhanced by rosiglitazone, an activating PPARγ ligand, in a PPARγ-dependent manner. Moreover, PPARγ is require...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.312355.118
更新日期：2018-08-01 00:00:00
abstract：:Somatic cell clones often fail at a developmental stage coincident with commencement of differentiation. The transcription factor Oct4 is expressed during cleavage stages and is essential for the differentiation of the blastocyst. Oct4 expression becomes restricted to the inner cell mass and epiblast. After gastrulati...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.966002
更新日期：2002-05-15 00:00:00
abstract：:During vascular development, endothelial platelet-derived growth factor B (PDGF-B) is critical for pericyte recruitment. Deletion of the conserved C-terminal heparin-binding motif impairs PDGF-BB retention and pericyte recruitment in vivo, suggesting a potential role for heparan sulfate (HS) in PDGF-BB function during...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.398207
更新日期：2007-02-01 00:00:00
abstract：:The Drosophila scratch (scrt) gene is expressed in most or all neuronal precursor cells and encodes a predicted zinc finger transcription factor closely related to the product of the mesoderm determination gene snail (sna). Adult flies homozygous for scrt null alleles have a reduced number of photoreceptors in the eye...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.9.19.2384
更新日期：1995-10-01 00:00:00
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
doi：10.1101/gad.10.23.2993
更新日期：1996-12-01 00:00:00
