Abstract:
:Drugs that produce covalent interstrand cross-links (ICLs) in DNA remain central to the treatment of cancer, but the cell cycle checkpoints activated by ICLs have received little attention. We have used the fission yeast, Schizosaccharomyces pombe, to elucidate the checkpoint responses to the ICL-inducing anticancer drugs nitrogen mustard and mitomycin C. First we confirmed that the repair pathways acting on ICLs in this yeast are similar to those in the main organisms studied to date (Escherichia coli, budding yeast, and mammalian cells), principally nucleotide excision repair and homologous recombination. We also identified and disrupted the S. pombe homologue of the Saccharomyces cerevisiae SNM1/PSO2 ICL repair gene and found that this activity is required for normal resistance to cross-linking agents, but not other forms of DNA damage. Survival and biochemical analysis indicated a key role for the "checkpoint Rad" family acting through the chk1-dependent DNA damage checkpoint in the ICL response. Rhp9-dependent phosphorylation of Chk1 correlates with G(2) arrest following ICL induction. In cells able to bypass the G(2) block, a second-cycle (S-phase) arrest was observed. Only a transient activation of the Cds1 DNA replication checkpoint factor occurs following ICL formation in wild-type cells, but this is increased and persists in G(2) arrest-deficient mutants. This likely reflects the fraction of cells escaping the G(2) damage checkpoint and arresting in the subsequent S phase due to ICL replication blocks. Disruption of cds1 confers increased resistance to ICLs, suggesting that this second-cycle S-phase arrest might be a lethal event.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Lambert S,Mason SJ,Barber LJ,Hartley JA,Pearce JA,Carr AM,McHugh PJdoi
10.1128/mcb.23.13.4728-4737.2003subject
Has Abstractpub_date
2003-07-01 00:00:00pages
4728-37issue
13eissn
0270-7306issn
1098-5549journal_volume
23pub_type
杂志文章abstract::The first processing event that mouse pre-rRNA undergoes occurs within the external transcribed spacer and is efficiently reproduced in vitro. Analysis with nondenaturing polyacrylamide gels revealed the formation of heparin-resistant complexes of retarded electrophoretic mobility on the substrate rRNA. The specificit...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.10.9.4920
更新日期:1990-09-01 00:00:00
abstract::In this report, we explored the mechanisms underlying keratinocyte-specific and differentiation-specific gene expression in the skin. We have identified five keratinocyte-specific, open chromatin regions that exist within the 6 kb of 5' upstream regulatory sequence known to faithfully recapitulate the strong endogenou...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.22.12.4293-4308.2002
更新日期:2002-06-01 00:00:00
abstract::The PH domain-containing proteins Slm1 and Slm2 were previously identified as effectors of the phosphatidylinositol-4,5-bisphosphate (PI4,5P(2)) and TORC2 signaling pathways. Here, we demonstrate that Slm1 and Slm2 are also targets of sphingolipid signaling during the heat shock response. We show that upon depletion o...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00461-06
更新日期:2007-01-01 00:00:00
abstract::The Saccharomyces cerevisiae mutant ref2-1 (REF = RNA end formation) was originally identified by a genetic strategy predicted to detect decreases in the use of a CYC1 poly(A) site interposed within the intron of an ACT1-HIS4 fusion reporter gene. Direct RNA analysis now proves this effect and also demonstrates the tr...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.15.3.1689
更新日期:1995-03-01 00:00:00
abstract::The expression of three different actin genes in the sea urchin, Strongylocentrotus purpuratus, was monitored in embryos and adult tissues by using untranslated mRNA sequences as specific hybridization probes. Three distinct patterns of expression were found: muscle specific, embryo specific, and constitutive (i.e., p...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.4.5.840
更新日期:1984-05-01 00:00:00
abstract::Acquisition of the ability to produce gamma interferon (IFN-gamma) is a fundamental property of memory T cells and enables one subset (T helper 1 [TH1]) to deliver its effector functions. To examine regulation of IFN-gamma gene expression in a model system which recapitulates TH1 differentiation, we prepared reporter ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.17.1.199
更新日期:1997-01-01 00:00:00
abstract::The hemagglutinin-neuraminidase (HN) protein of paramyxoviruses is likely in the unusual class of glycoproteins with the amino terminus cytoplasmic and the carboxy terminus lumenal or external to the cell. The properties of the membrane insertion of the HN protein of Newcastle disease virus, a prototype paramyxovirus,...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.7.4.1386
更新日期:1987-04-01 00:00:00
abstract::Prdm1/Blimp-1 is a master regulator of gene expression in diverse tissues of the developing embryo and adult organism. Its C-terminal zinc finger domain mediates nuclear import, DNA binding, and recruitment of the corepressors G9a and HDAC1/2. Alternatively spliced transcripts lacking exon 7 sequences encode a structu...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00174-12
更新日期:2012-09-01 00:00:00
abstract::A protein that binds specifically to Saccharomyces cerevisiae centromere DNA element I was purified on the basis of a nitrocellulose filter-binding assay. This protein, termed centromere-binding protein 1 (CP1), was heat stable and renaturable from sodium dodecyl sulfate (SDS), and assays of eluates from SDS gels indi...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.7.1.403
更新日期:1987-01-01 00:00:00
abstract::In this report we described the cloning and characterization of ADA5, a gene identified by resistance to GAL4-VP16-mediated toxicity. ADA5 binds directly to the VP16 activation domain but not to a transcriptionally defective VP16 double point mutant. Double mutants with mutations in ada5 and other genes (ada2 or ada3)...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.16.6.3197
更新日期:1996-06-01 00:00:00
abstract::The C-terminal domain of the RNA polymerase II largest subunit (the Rpb1 CTD) is composed of tandem heptad repeats of the consensus sequence Y(1)S(2)P(3)T(4)S(5)P(6)S(7). We reported previously that Thr 4 is phosphorylated and functions in histone mRNA 3'-end formation in chicken DT40 cells. Here, we have extended our...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00181-14
更新日期:2014-07-01 00:00:00
abstract::Mammalian cells were observed to die under conditions in which nutrients were depleted and, simultaneously, macroautophagy was inhibited either genetically (by a small interfering RNA targeting Atg5, Atg6/Beclin 1-1, Atg10, or Atg12) or pharmacologically (by 3-methyladenine, hydroxychloroquine, bafilomycin A1, or mone...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.3.1025-1040.2005
更新日期:2005-02-01 00:00:00
abstract::Ligand activation of Notch receptors leads to release of the intracellular receptor domain (Notch IC), which translocates to the nucleus and interacts with the DNA-binding protein RBP-Jkappa to control expression of specific target genes. A number of proteins have been shown to interact with Notch ICs and to modulate ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.22.22.7812-7819.2002
更新日期:2002-11-01 00:00:00
abstract::Expression of the acute-phase response genes, such as that for alpha-1 acid glycoprotein (AGP), involves both positive and negative transcription factors. A positive transcription factor, AGP/EBP, and a negative transcription factor, factor B, have been identified as the two most important factors responsible for the ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.9.6068
更新日期:1994-09-01 00:00:00
abstract::Endonuclease decay of nonsense-containing beta-globin mRNA in erythroid cells generates 5'-truncated products that were reported previously to have a cap or caplike structure. We confirmed that this 5' modification is indistinguishable from the cap on full-length mRNA, and Western blotting, immunoprecipitation, and ac...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01325-08
更新日期:2009-04-01 00:00:00
abstract::The murine lambda5-VpreB1 locus encodes two proteins that form part of the pre-B-cell receptor and play a key role in B-lymphocyte development. We have identified a locus control region (LCR) which is responsible for coordinate activation of both genes in pre-B cells. Analysis of mice with single and multiple copies o...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.19.1.671
更新日期:1999-01-01 00:00:00
abstract::The 54K cellular tumor antigen has been translated in vitro, using messenger ribonucleic acids from simian virus 40 (SV40)-transformed cells or 3T3 cells. The in vitro 54K product could be immunoprecipitated with SV40 tumor serum and had a peptide map that was similar, but not identical, to the in vivo product. The le...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.1.2.101
更新日期:1981-02-01 00:00:00
abstract::We constructed a series of recombinant genomes which directed expression of the enzyme chloramphenicol acetyltransferase (CAT) in mammalian cells. The prototype recombinant in this series, pSV2-cat, consisted of the beta-lactamase gene and origin of replication from pBR322 coupled to a simian virus 40 (SV40) early tra...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.2.9.1044
更新日期:1982-09-01 00:00:00
abstract::In Saccharomyces cerevisiae, pseudouridine formation in the middle position of the tRNA(Tyr) anticodon (psi 35) is dependent on the presence of the intron in the tRNA(Tyr) gene (Johnson and Abelson, Nature 302:681-687, 1983). Drosophila melanogaster tRNA(Tyr) genes contain introns of three size classes: 20 or 21 base ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.8.8.3332
更新日期:1988-08-01 00:00:00
abstract::The MyoD gene can orchestrate the expression of the skeletal muscle differentiation program. We have identified the regions of the gene necessary to reproduce transcription specific to skeletal myoblasts and myotubes. A proximal regulatory region (PRR) contains a conserved TATA box, a CCAAT box, and a GC-rich region t...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.12.11.4994
更新日期:1992-11-01 00:00:00
abstract::Activation of multiple signaling pathways is required to trigger the full spectrum of in vitro and in vivo phenotypic traits associated with neoplastic transformation by oncogenic Ras. To determine which of these pathways are important for N-ras tumorigenesis in human cancer cells and also to investigate the possibili...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.20.24.9294-9306.2000
更新日期:2000-12-01 00:00:00
abstract::It has previously been demonstrated that the simian virus 40 large T antigen and adenovirus E1A proteins can form complexes with the retinoblastoma susceptibility gene product (RB). We studied the ability of these proteins to bind to mutant RB proteins in vitro. A region of RB spanning residues 379 to 792 was found to...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.10.7.3761
更新日期:1990-07-01 00:00:00
abstract::The full-length normal and T24 mutant human H-ras proteins and two truncated derivatives of the T24 mutant were expressed efficiently in Escherichia coli. The proteins accumulated to 1 to 5% of total cellular protein, and each was specifically recognized by anti-ras monoclonal antibodies. The two full-length proteins ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.5.5.1015
更新日期:1985-05-01 00:00:00
abstract::Enhancer elements modulate promoter activity over vast chromosomal distances, and mechanisms that ensure restrictive interactions between promoters and enhancers are critical for proper control of gene expression. The human beta-globin locus control region (LCR) activates expression of five genes in erythroid cells, i...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00602-07
更新日期:2007-08-01 00:00:00
abstract::Sophisticated models for the regulation of mitotic entry are lacking for human cells. Inactivating human cyclin A/Cdk2 complexes through diverse approaches delays mitotic entry and promotes inhibitory phosphorylation of Cdk1 on tyrosine 15, a modification performed by Wee1. We show here that cyclin A/Cdk2 complexes ph...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01876-08
更新日期:2010-01-01 00:00:00
abstract::The ligand-binding domains of thyroid hormone (L-triiodothyronine [T3]) receptors (T3Rs), all-trans retinoic acid (RA) receptors (RARs), and 9-cis RA receptors (RARs and RXRs) contain a series of heptad motifs thought to be important for dimeric interactions. Using a chimera containing amino acids 120 to 392 of chicke...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.9.5756
更新日期:1994-09-01 00:00:00
abstract::In this study, we have constructed retroviral vectors expressing the interleukin-7 (IL-7) cDNA and have used infection with these retroviruses to express this cytokine endogenously in an IL-7-dependent pre-B-cell line. Infection with IL-7 retroviruses, but not with a control retrovirus, resulted in the conversion of t...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.11.3.1590
更新日期:1991-03-01 00:00:00
abstract::In the budding yeast Saccharomyces cerevisiae, Cdc37 is required for the productive formation of Cdc28-cyclin complexes. The cdc37-1 mutant arrests at Start with low levels of Cdc28 protein, which is predominantly unphosphorylated at Thr169, fails to bind cyclin, and has little protein kinase activity. We show here th...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.20.3.749-754.2000
更新日期:2000-02-01 00:00:00
abstract::GIPC is a PDZ protein located on peripheral endosomes that binds to the juxtamembrane region of the TrkA nerve growth factor (NGF) receptor and has been implicated in NGF signaling. We establish here that endogenous GIPC binds to the C terminus of APPL, a Rab5 binding protein, which is a marker for signaling endosomes...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00305-06
更新日期:2006-12-01 00:00:00
abstract::The tumor suppressor protein ARF inhibits MDM2 to activate and stabilize p53. Recent studies provided evidence for p53-independent tumor suppression functions of ARF. For example, it has been shown that ARF induces proteolysis of certain E2F species, including E2F1. In addition, ARF relocalizes E2F1 from the nucleopla...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.22.24.8398-8408.2002
更新日期:2002-12-01 00:00:00