Abstract:
:How dividing mammalian cells overcome blocks to DNA replication by DNA damage, depleted nucleotide pools, or template-bound proteins is unclear. Here, we show that the response to blocked replication requires BRCA2, a suppressor of human breast cancer. By using two-dimensional gel electrophoresis, we demonstrate that Y-shaped DNA junctions at stalled replication forks disappear during genome-wide replication arrest in BRCA2-deficient cells, accompanied by double-strand DNA breakage. But activation of the replication checkpoint kinase Chk2 is unaffected, defining an unexpected function for BRCA2 in stabilizing DNA structures at stalled forks. We propose that in BRCA2 deficiency and related chromosomal instability diseases, the breakdown of replication forks, which arrest or pause during normal cell growth, triggers spontaneous DNA breakage, leading to mutability and cancer predisposition.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Lomonosov M,Anand S,Sangrithi M,Davies R,Venkitaraman ARdoi
10.1101/gad.279003subject
Has Abstractpub_date
2003-12-15 00:00:00pages
3017-22issue
24eissn
0890-9369issn
1549-5477pii
279003journal_volume
17pub_type
杂志文章abstract::rhomboid (rho) belongs to a group of four genes involved in the elaboration of positional information at a ventrolateral level in the Drosophila embryo. Mutations at any of these four loci also lead to a variety of other phenotypes, including reduction in the number of stretch receptor organs (chordotonal organs) in t...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.4.2.190
更新日期:1990-02-01 00:00:00
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
doi:10.1101/gad.1751109
更新日期:2009-03-01 00:00:00
abstract::Activated transcription by RNA polymerase II (Pol II) requires coactivators, one of which is the SRB/mediator. Whereas Srb4, an essential subunit of the SRB/mediator, is broadly required for Pol II transcription in yeast, we have shown that it is dispensable for the transcriptional activation of some genes. Here, we s...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.13.22.2934
更新日期:1999-11-15 00:00:00
abstract::The organizer region, or dorsal blastopore lip, plays a central role in the initiation of gastrulation and the formation of the body axis during Xenopus development. A similar process can also be induced in ectodermal explants by activin or by injection of activin mRNA into embryos. We have searched early embryo-speci...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.6.4.599
更新日期:1992-04-01 00:00:00
abstract::The PWI motif is a highly conserved domain of unknown function in the SRm160 splicing and 3'-end cleavage-stimulatory factor, as well as in several other known or putative pre-mRNA processing components. We show here that the PWI motif is a new type of RNA/DNA-binding domain that has an equal preference for single- an...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1060403
更新日期:2003-02-15 00:00:00
abstract::Genome instability is a recurring feature of tumorigenesis. Mutation in MLL2, encoding a histone methyltransferase, is a driver in numerous different cancer types, but the mechanism is unclear. Here, we present evidence that MLL2 mutation results in genome instability. Mouse cells in which MLL2 gene deletion can be in...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.275453.115
更新日期:2016-02-15 00:00:00
abstract::The Dorsal morphogen is a transcription factor that activates some genes and represses others to establish multiple domains of gene expression along the dorsal/ventral axis of the early Drosophila embryo. Repression by Dorsal appears to require accessory proteins that bind to corepression elements in Dorsal-dependent ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.9.24.3177
更新日期:1995-12-15 00:00:00
abstract::VASA is an evolutionarily conserved RNA helicase essential for germ cell development. The mouse PIWI family proteins MILI and MIWI2 are involved in production of Piwi-interacting RNAs (piRNAs) in fetal male germ cells through a ping-pong amplification cycle. Expression of retrotransposons is elevated in MILI- and MIWI...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1902110
更新日期:2010-05-01 00:00:00
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
doi:10.1101/gad.3.7.1062
更新日期:1989-07-01 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::Natural scrapie has been viewed both as a recessive trait and as a contagious disease modulated by a host locus. To address this conundrum, we determined the structure of the sheep prion protein (PrP) gene, which contains three exons and extends over 20 kb of DNA. In the United States 86.4% of scrapie cases occur in S...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.8.8.959
更新日期:1994-04-15 00:00:00
abstract::The formins constitute a set of protein isoforms encoded by the alternatively spliced transcripts arising from the limb deformity (ld) locus of the mouse. Mutations in this locus disrupt formation of the anteroposterior axis of the embryonic limb. Although ld transcripts are widely expressed during embryogenesis, we h...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.6.1.29
更新日期:1992-01-01 00:00:00
abstract::The N-myc gene encodes a putative transcription factor that is thought to function in the regulation of gene expression during cell differentiation and/or growth. To examine the role of N-myc during development, we have used targeted mutagenesis in embryonic stem cells to produce a mouse line that carries an N-myc nul...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.6.12a.2248
更新日期:1992-12-01 00:00:00
abstract::Multidimensional cancer genome analysis and validation has defined Quaking (QKI), a member of the signal transduction and activation of RNA (STAR) family of RNA-binding proteins, as a novel glioblastoma multiforme (GBM) tumor suppressor. Here, we establish that p53 directly regulates QKI gene expression, and QKI prote...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.189001.112
更新日期:2012-07-01 00:00:00
abstract::The Swi/Snf chromatin remodeling complex functions to alter nucleosome positions by either sliding nucleosomes on DNA or the eviction of histones. The presence of histone acetylation and activator-dependent recruitment and retention of Swi/Snf is important for its efficient function. It is not understood, however, why...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.243584.114
更新日期:2014-10-15 00:00:00
abstract::The choice of self-renewal versus differentiation is a fundamental issue in stem cell and cancer biology. Neural progenitors of the Drosophila post-embryonic brain, larval neuroblasts (NBs), divide asymmetrically in a stem cell-like fashion to generate a self-renewing NB and a Ganglion Mother Cell (GMC), which divides...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1487506
更新日期:2006-12-15 00:00:00
abstract::Class Ia phosphatidylinositol 3 kinase (PI3K) is required for oncogenic receptor-mediated transformation; however, the individual roles of the two commonly expressed class Ia PI3K isoforms in oncogenic receptor signaling have not been elucidated in vivo. Here, we show that genetic ablation of p110α blocks tumor format...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.191973.112
更新日期:2012-07-15 00:00:00
abstract::The histone variants H3.3 and H2A.Z have recently emerged as two of the most important features in transcriptional regulation, the molecular mechanism of which still remains poorly understood. In this study, we investigated the regulation of H3.3 and H2A.Z on chromatin dynamics during transcriptional activation. Our i...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.222174.113
更新日期:2013-10-01 00:00:00
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
doi:10.1101/gad.1790409
更新日期:2009-05-01 00:00:00
abstract::Placental development is profoundly influenced by oxygen (O(2)) tension. Human cytotrophoblasts proliferate in vitro under low O(2) conditions but differentiate at higher O(2) levels, mimicking the developmental transition they undergo as they invade the placental bed to establish the maternal-fetal circulation in viv...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.853700
更新日期:2000-12-15 00:00:00
abstract::Symbiotic nitrogen fixation involves the development of specialized organs called nodules within which plant photosynthates are exchanged for combined nitrogen of bacterial origin. To determine the importance of bacterial nitrogen metabolism in symbiosis, we have characterized a key regulator of this metabolism in Rhi...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.11.9.1194
更新日期:1997-05-01 00:00:00
abstract::Bistability in developmental pathways refers to the generation of binary outputs from graded or noisy inputs. Signaling thresholds are critical for bistability. Specification of the left/right (LR) axis in vertebrate embryos involves bistable expression of transforming growth factor beta (TGFbeta) member NODAL in the ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1682108
更新日期:2008-11-01 00:00:00
abstract::The association of proteins with the branch site region during pre-mRNA splicing was probed using a novel methodology to site-specifically modify the pre-mRNA with the photo-reagent benzophenone. Three sets of proteins were distinguished by the kinetics of their associations with pre-mRNAs, by their association with d...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.8.24.3008
更新日期:1994-12-15 00:00:00
abstract::In this issue of Genes & Development, Dowen and colleagues (pp. 1515-1528) elegantly unify two previously unconnected aspects of physiology. The investigators provide significant genetic evidence to support a critical link between developmental timing decisions and the regulation of lipid mobilization at the transitio...
journal_title:Genes & development
pub_type: 评论,杂志文章
doi:10.1101/gad.285460.116
更新日期:2016-07-01 00:00:00
abstract::Male sexual development in the nematode Caenorhabditis elegans requires the genes fem-1, fem-2, and fem-3. The current model of sex determination portrays the FEM proteins as components of a novel signal transduction pathway, but the mechanisms involved in signaling through the pathway are not understood. We report th...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.10.18.2314
更新日期:1996-09-15 00:00:00
abstract::Chromosome segregation requires stable bipolar attachments of spindle microtubules to kinetochores. The dynein/dynactin motor complex localizes transiently to kinetochores and is implicated in chromosome segregation, but its role remains poorly understood. Here, we use the Caenorhabditis elegans embryo to investigate ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1687508
更新日期:2008-09-01 00:00:00
abstract::Cell for cell, probably no human cancer is as aggressive as melanoma. It is among a handful of cancers whose dimensions are reported in millimeters. Tumor thickness approaching 4 mm presents a high risk of metastasis, and a diagnosis of metastatic melanoma carries with it an abysmal median survival of 6-9 mo. What fea...
journal_title:Genes & development
pub_type: 杂志文章,评审
doi:10.1101/gad.1437206
更新日期:2006-08-15 00:00:00
abstract::Direct reprogramming of fibroblasts to cardiomyocytes represents a potential means of restoring cardiac function following myocardial injury. AKT1 in the presence of four cardiogenic transcription factors, GATA4, HAND2, MEF2C, and TBX5 (AGHMT), efficiently induces the cardiac gene program in mouse embryonic fibroblast...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.305482.117
更新日期:2017-09-01 00:00:00
abstract::The mechanisms by which homeoproteins bind selectively to target genes in vivo have long remained unresolved. Here we report that PIAS1 confers DNA-binding specificity on the Msx1 homeoprotein by regulating its subnuclear localization and proximity to target genes. We demonstrate that the interaction of Msx1 with PIAS...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1392006
更新日期:2006-04-01 00:00:00
abstract::The sigma(28) protein is a member of the bacterial sigma(70)-family of transcription factors that directs RNA polymerase to flagellar late (class 3) promoters. The sigma(28) protein is regulated in response to flagellar assembly by the anti-sigma(28) factor FlgM. FlgM inhibits sigma(28)-dependent transcription of gene...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.380406
更新日期:2006-08-15 00:00:00