Abstract:
:Faithful duplication of the genome relies on the ability to cope with an imperfect template. We investigated replication of UV-damaged DNA in Escherichia coli and found that ongoing replication stops for at least 15-20 min before resuming. Undamaged origins of replication (oriC) continue to fire at the normal rate and in a DnaA-dependent manner. UV irradiation also induces substantial DnaA-independent replication. These two factors add substantially to the DNA synthesis detected after irradiation and together mask the delay in the progression of pre-existing forks in assays measuring net synthesis. All DNA synthesis after UV depends on DnaC, implying that replication restart of blocked forks requires DnaB loading and possibly the entire assembly of new replisomes. Restart appears to occur synchronously when most lesions have been removed. This raises the possibility that restart and lesion removal are coupled. Both restart and cell division suffer long delays if lesion removal is prevented, but restart can occur. Our data fit well with models invoking the stalling of replication forks and their extensive processing before replication can restart. Delayed restart avoids the dangers of excessive recombination that might result if forks skipped over lesion after lesion, leaving many gaps in their wake.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Rudolph CJ,Upton AL,Lloyd RGdoi
10.1101/gad.417607subject
Has Abstractpub_date
2007-03-15 00:00:00pages
668-81issue
6eissn
0890-9369issn
1549-5477pii
21/6/668journal_volume
21pub_type
杂志文章abstract::The growth suppression function of the retinoblastoma protein (RB) is mediated by its interaction with a variety of cellular proteins. RB contains at least two protein-binding pockets: the large A/B pocket, which interacts with E2F and the D-type cyclins, and the C pocket, which interacts with the nuclear c-Abl tyrosi...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.9.1.31
更新日期:1995-01-01 00:00:00
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
doi:10.1101/gad.2.7.843
更新日期:1988-07-01 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
abstract::Genome-wide association studies (GWASs) have identified a genetic variant of moderate effect size at 6p21.1 associated with erythrocyte traits in humans. We show that this variant affects an erythroid-specific enhancer of CCND3. A Ccnd3 knockout mouse phenocopies these erythroid phenotypes, with a dramatic increase in...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.197020.112
更新日期:2012-09-15 00:00:00
abstract::Previous characterization of the Saccharomyces cerevisiae Spt4, Spt5, and Spt6 proteins suggested that these proteins act as transcription factors that modify chromatin structure. In this work, we report new genetic and biochemical studies of Spt4, Spt5, and Spt6 that reveal a role for these factors in transcription e...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.12.3.357
更新日期:1998-02-01 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::Inactivation of cyclin B-Cdc2 kinase at the exit from M phase depends on the specific proteolysis of the cyclin B subunit, whereas the Cdc2 subunit remains present at nearly constant levels throughout the cell cycle. It is unknown how Cdc2 escapes degradation when cyclin B is destroyed. In Xenopus egg extracts that re...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.823200
更新日期:2000-09-15 00:00:00
abstract::Studying the early stages of cancer can provide important insight into the molecular basis of the disease. We identified a preneoplastic stage in the patched (ptc) mutant mouse, a model for the brain tumor medulloblastoma. Preneoplastic cells (PNCs) are found in most ptc mutants during early adulthood, but only 15% of...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1759909
更新日期:2009-01-15 00:00:00
abstract::The Snail zinc-finger transcription factors trigger epithelial-mesenchymal transitions (EMTs), endowing epithelial cells with migratory and invasive properties during both embryonic development and tumor progression. During EMT, Snail provokes the loss of epithelial markers, as well as changes in cell shape and the ex...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.294104
更新日期:2004-05-15 00:00:00
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
doi:10.1101/gad.248245.114
更新日期:2014-12-01 00:00:00
abstract::Transabdominal (Tab), a dominant mutation in the Bithorax Complex (BX-C) of Drosophila, creates a sexually dimorphic pattern of segmental transformation that has complete penetrance and expressivity. Specific regions within the notum of the second thoracic segment (T2) are transformed into abdominal-like cuticle; thus...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1.2.111
更新日期:1987-04-01 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::Recombination catalyzed by the Flp site-specific recombinase involves breakage and joining of four DNA strands between two target substrates. The reaction is carried out in two steps of pairwise strand exchanges by a DNA-protein assembly in which four Flp monomers act cooperatively to execute strand cleavage and joini...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.11.18.2438
更新日期:1997-09-15 00:00:00
abstract::All multisubunit DNA-dependent RNA polymerases (RNAP) are zinc metalloenzymes, and at least two zinc atoms are present per enzyme molecule. RNAP residues involved in zinc binding and the functional role of zinc ions in the transcription mechanism or RNAP structure are unknown. Here, we locate four cysteine residues in...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.13.18.2439
更新日期:1999-09-15 00:00:00
abstract::Oncogene-induced senescence (OIS) is a potent tumor suppressor mechanism. To identify senescence regulators relevant to cancer, we screened an shRNA library targeting genes deleted in hepatocellular carcinoma (HCC). Here, we describe how knockdown of the SWI/SNF component ARID1B prevents OIS and cooperates with RAS to...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.286112.116
更新日期:2016-10-01 00:00:00
abstract::Many short-lived mRNAs, including those encoding lymphokines, cytokines, and proto-oncogenes, contain an AU-rich sequence in their 3'-untranslated regions. These AU domains and, more specifically, AUUUA motifs within them, are widely thought to mediate the extreme instability of the corresponding mRNAs. This is most c...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.6.10.1927
更新日期:1992-10-01 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::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::The mechanisms that determine the relative positions of floral organs, and thereby their numbers, is a poorly understood aspect of flower development. We isolated a petunia mutant, floozy (fzy), in which the formation of floral organ primordia in the outermost three floral whorls and one of the two bracts at the base ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.219502
更新日期:2002-03-15 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::GRF2, an abundant yeast protein of Mr approximately 127,000, binds to the GAL upstream activating sequence (UASG) and creates a nucleosome-free region of approximately 230 bp. Purified GRF2 binds to sequences found in many other UASs, in the 35S rRNA enhancer, at centromeres, and at telomeres. Although GRF2 stimulates...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.4.4.503
更新日期:1990-04-01 00:00:00
abstract::Transcription factor IIA has been shown to interact with the TATA-binding protein and to act early during preinitiation complex formation. The human factor is composed of three subunits (alpha, beta, gamma). A human cDNA clone encoding the largest subunit of TFIIA (alpha) was isolated. The recombinant alpha polypeptid...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.7.11.2246
更新日期:1993-11-01 00:00:00
abstract::Cell growth and differentiation are usually antagonistic. Proteins of the basic helix-loop-helix (bHLH) family bind DNA and play important roles in the differentiation of specific cell types. Id proteins heterodimerize with bHLH transcription factors, blocking their activation of lineage-specific gene expression and t...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.8.11.1270
更新日期:1994-06-01 00:00:00
abstract::Multiple DNA repair pathways maintain genome stability and ensure that DNA remains essentially unchanged over the life of a cell. Various human diseases occur if DNA repair is compromised, and most of these impact the nervous system, in some cases exclusively. However, it is often unclear what specific endogenous dama...
journal_title:Genes & development
pub_type: 杂志文章,评审
doi:10.1101/gad.301325.117
更新日期:2017-06-15 00:00:00
abstract::Regions on the surface of human TATA-box binding protein (TBP) required for activated transcription in vivo were defined by construction of a library of 89 surface residue mutants with radical substitutions that were assayed for their ability to support activated transcription in vivo, basal transcription in vitro, an...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.10.19.2491
更新日期:1996-10-01 00:00:00
abstract::Transcription factors represent one of the largest groups of proteins regulated by SUMO (small ubiquitin-like modifier) modification, and their sumoylation is usually associated with transcriptional repression. To investigate whether sumoylation plays a general role in regulating transcription in yeast, we determined ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1917910
更新日期:2010-06-15 00:00:00
abstract::Persistent DNA double-strand breaks and telomeres represent genomic hazards, as they can instigate inappropriate repair reactions. Two recent papers by Oza and colleagues (pp. 912-917) and Schober and colleagues (pp. 928-938) show that both types of DNA ends are sequestered from bulk DNA by Mps3, a SUN domain protein ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1805309
更新日期:2009-05-01 00:00:00
abstract::The c-fos serum response element (SRE) is a multifunctional regulatory region of the c-fos promoter that responds to a variety of inducers. Recently, we have demonstrated that the SRE binds the C/EBP-related transcription factor rat NFIL-6 (rNFIL-6). In this study we show that rNFIL-6 is regulated by the cAMP second m...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.5.10.1754
更新日期:1991-10-01 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::Translation initiation factor 2 (eIF2) bound to GTP transfers the initiator methionyl tRNA to the 40S ribosomal subunit. The eIF5 stimulates GTP hydrolysis by the eIF2/GTP/Met-tRNA(i)(Met) ternary complex on base-pairing between Met-tRNA(i)(Met) and the start codon. The eIF2, eIF5, and eIF1 all have been implicated in...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.831800
更新日期:2000-10-01 00:00:00