Abstract:
:Telomeres are essential for protecting the ends of chromosomes and preventing chromosome fusion. Telomere loss has been proposed to play an important role in the chromosomal rearrangements associated with tumorigenesis. To determine the relationship between telomere loss and chromosome instability in mammalian cells, we investigated the events resulting from the introduction of a double-strand break near a telomere with I-SceI endonuclease in mouse embryonic stem cells. The inactivation of a selectable marker gene adjacent to a telomere as a result of the I-SceI-induced double-strand break involved either the addition of a telomere at the site of the break or the formation of inverted repeats and large tandem duplications on the end of the chromosome. Nucleotide sequence analysis demonstrated large deletions and little or no complementarity at the recombination sites involved in the formation of the inverted repeats. The formation of inverted repeats was followed by a period of chromosome instability, characterized by amplification of the subtelomeric region, translocation of chromosomal fragments onto the end of the chromosome, and the formation of dicentric chromosomes. Despite this heterogeneity, the rearranged chromosomes eventually acquired telomeres and were stable in most of the cells in the population at the time of analysis. Our observations are consistent with a model in which broken chromosomes that do not regain a telomere undergo sister chromatid fusion involving nonhomologous end joining. Sister chromatid fusion is followed by chromosome instability resulting from breakage-fusion-bridge cycles involving the sister chromatids and rearrangements with other chromosomes. This process results in highly rearranged chromosomes that eventually become stable through the addition of a telomere onto the broken end. We have observed similar events after spontaneous telomere loss in a human tumor cell line, suggesting that chromosome instability resulting from telomere loss plays a role in chromosomal rearrangements associated with tumor cell progression.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Lo AW,Sprung CN,Fouladi B,Pedram M,Sabatier L,Ricoul M,Reynolds GE,Murnane JPdoi
10.1128/mcb.22.13.4836-4850.2002subject
Has Abstractpub_date
2002-07-01 00:00:00pages
4836-50issue
13eissn
0270-7306issn
1098-5549journal_volume
22pub_type
杂志文章abstract::C3G, which was identified as a Crk SH3 domain-binding guanine nucleotide-releasing factor, shows sequence similarity to CDC25 and Sos family proteins (S. Tanaka, T. Morishita, Y. Hashimoto, S. Hattori, S. Nakamura, M. Shibuya, K. Matuoka, T. Takenawa, T. Kurata, K. Nagashima, and M. Matsuda, Proc. Natl. Acad. Sci. USA...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.15.12.6746
更新日期:1995-12-01 00:00:00
abstract::SH2 (src homology region 2) domains are implicated in protein-protein interactions involved in signal transduction pathways. Isolated SH2 domains bind proteins that are tyrosine phosphorylated. A novel, phosphotyrosine-independent binding interaction between BCR, the Philadelphia chromosome breakpoint cluster region g...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.12.11.5087
更新日期:1992-11-01 00:00:00
abstract::Tax1, a potent activator of human T-cell lymphotropic virus type 1 (HTLV-1) transcription, has been shown to modulate expression of many cellular genes. Tax1 does not bind DNA directly but regulates transcription through protein-protein interactions with sequence-specific transcription factors. Using the yeast two-hyb...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.17.3.1236
更新日期:1997-03-01 00:00:00
abstract::Numerous studies indirectly implicate Rac GTPases in cancer. To investigate if Rac3 contributes to normal or malignant cell function, we generated rac3 null mutants through gene targeting. These mice were viable, fertile, and lacked an obvious external phenotype. This shows Rac3 function is dispensable for embryonic d...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.13.5777-5785.2005
更新日期:2005-07-01 00:00:00
abstract::To examine the functional role of the interaction between Munc18c and syntaxin 4 in the regulation of GLUT4 translocation in 3T3L1 adipocytes, we assessed the effects of introducing three different peptide fragments (20 to 24 amino acids) of Munc18c from evolutionarily conserved regions of the Sec1 protein family pred...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.20.1.379-388.2000
更新日期:2000-01-01 00:00:00
abstract::Hes1 is a mammalian basic helix-loop-helix transcriptional repressor that inhibits neuronal differentiation together with corepressors of the Groucho (Gro)/Transducin-like Enhancer of split (TLE) family. The interaction of Hes1 with Gro/TLE is mediated by a WRPW tetrapeptide present in all Hairy/Enhancer of split (Hes...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.23.19.6922-6935.2003
更新日期:2003-10-01 00:00:00
abstract::Signaling via the pre-T-cell receptor (pre-TCR), along with associated signals from Notch and chemokine receptors, regulates the β-selection checkpoint that operates on CD4(-) CD8(-) doubly negative (DN) thymocytes. Since many hematopoietic malignancies arise at the immature developmental stages of lymphocytes, unders...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01084-14
更新日期:2015-04-01 00:00:00
abstract::The ALCR protein is the transcriptional activator of the ethanol utilization pathway in the filamentous fungus Aspergillus nidulans. This activator belongs to a family of fungal proteins having a conserved DNA-binding domain containing six cysteines (C6 class) with some striking features. At variance with other motifs...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.12.5.1932
更新日期:1992-05-01 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::One of the proteins identified as being involved in ribosome biogenesis by high-throughput studies, a putative P-loop-type kinase termed Fap7 (YDL166c), was shown to be required for the conversion of 20S pre-rRNA to 18S rRNA. However, the mechanism underlying this function has remained unclear. Here we demonstrate tha...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.23.10352-10364.2005
更新日期:2005-12-01 00:00:00
abstract::The FLP protein of the Saccharomyces cerevisiae plasmid 2 microns circle catalyzes site-specific recombination between two repeated segments present on the plasmid. In this paper we present results of experiments we performed to define more precisely the features of the FLP recognition target site, which we propose to...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.6.10.3357
更新日期:1986-10-01 00:00:00
abstract::Axin is a recently identified protein encoded by the fused locus in mice that is required for normal vertebrate axis formation. We have defined a 25-amino-acid sequence in axin that comprises the glycogen synthase kinase 3beta (GSK-3beta) interaction domain (GID). In contrast to full-length axin, which has been shown ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.19.10.7147
更新日期:1999-10-01 00:00:00
abstract::We have isolated and subcloned three separate segments of human DNA which share strong sequence homology with a previously sequenced gene encoding a type I keratin, K14 (50 kilodaltons). Restriction endonuclease mapping has demonstrated that these three genes are tightly linked chromosomally, whereas the K14 gene appe...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.6.2.539
更新日期:1986-02-01 00:00:00
abstract::We utilized the mouse mammary tumor virus (MMTV) long terminal repeat (LTR) in vivo to understand how the interaction of the glucocorticoid receptor (GR) with a nucleosome-assembled promoter allows access of factors required for the transition from a repressed promoter to a derepressed, transcriptionally competent pro...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.19.12.8146
更新日期:1999-12-01 00:00:00
abstract::The transcriptional corepressor mSin3 is associated with histone deacetylases (HDACs) and is utilized by many DNA-binding transcriptional repressors. We have cloned and characterized a novel mSin3A-binding protein, SAP25. SAP25 binds to the PAH1 domain of mSin3A, associates with the mSin3A-HDAC complex in vivo, and re...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.26.4.1386-1397.2006
更新日期:2006-02-01 00:00:00
abstract::We report a negative feedback loop between the signaling protein phospholipase D (PLD), phosphatidic acid (PA), and a specific set of microRNAs (miRNAs) during nutrient starvation of breast cancer cells. We show that PLD expression is increased in four breast cancer cell lines and that hypoxia, cell overcrowding, and ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00711-15
更新日期:2016-01-19 00:00:00
abstract::SLC5A8 is a putative tumor suppressor that is inactivated in more than 10 different types of cancer, but neither the oncogenic signaling responsible for SLC5A8 inactivation nor the functional relevance of SLC5A8 loss to tumor growth has been elucidated. Here, we identify oncogenic HRAS (HRAS(G12V)) as a potent mediato...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01702-12
更新日期:2013-10-01 00:00:00
abstract::We previously identified an RNA binding protein, CUGBP1, which binds to GCN repeats located within the 5' region of C/EBPbeta mRNAs and regulates translation of C/EBPbeta isoforms. To further investigate the role of RNA binding proteins in the posttranscriptional control of C/EBP proteins, we purified additional RNA b...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.22.20.7242-7257.2002
更新日期:2002-10-01 00:00:00
abstract::A tetracycline-regulated reporter system was used to investigate the regulation of cyclooxygenase 2 (Cox-2) mRNA stability by the mitogen-activated protein kinase (MAPK) p38 signaling cascade. The stable beta-globin mRNA was rendered unstable by insertion of the 2, 500-nucleotide Cox-2 3' untranslated region (3' UTR)....
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.20.12.4265-4274.2000
更新日期:2000-06-01 00:00:00
abstract::The neutral/neutral two-dimensional (2-D) gel replicon mapping technique has been used to great advantage to localize and characterize origins of replication. Interestingly, many yeast origins display a composite pattern consisting of both a bubble arc and a single-fork arc. Moreover, in every instance in which neutra...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.16.9.4915
更新日期:1996-09-01 00:00:00
abstract::CCN2/CTGF is a multifunctional factor that plays a crucial role in the growth and differentiation of chondrocytes. The chicken ccn2 gene is regulated not only at the transcriptional level but also by the interaction between a posttranscriptional element in the 3' untranslated region (3'-UTR) and a cofactor. In the pre...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00495-08
更新日期:2008-10-01 00:00:00
abstract::Mutations in the SRA1 or SRA3 gene eliminate the requirement for either RAS gene (RAS1 or RAS2) in Saccharomyces cerevisiae. We cloned SRA1 and SRA3 and determined their DNA sequences. SRA1 encodes the regulatory subunit of the cyclic AMP (cAMP)-dependent protein kinase and therefore is identical to REG1 and BCY1. Thi...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.7.8.2653
更新日期:1987-08-01 00:00:00
abstract::A gene assigned to human chromosome 1q32-41 encodes a novel protein of 3,113 amino acids containing an internal tandem repeat of 177 amino acids. The protein, which we have named "mitosin," was identified by direct binding to purified retinoblastoma protein in vitro with a region distantly related to the retinoblastom...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.15.9.5017
更新日期:1995-09-01 00:00:00
abstract::The retinoblastoma tumor suppressor protein (Rb) plays a vital role in regulating mammalian cell cycle progression and inactivation of Rb is necessary for entry into S phase. Rb is inactivated by phosphorylation upon growth factor stimulation of quiescent cells, facilitating the transition from G(1) phase to S phase. ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.24.21.9527-9541.2004
更新日期:2004-11-01 00:00:00
abstract::DHCR24/seladin-1, a crucial enzyme in sterol synthesis, is of lower abundance in brain areas affected by Alzheimer's disease. While high levels of DHCR24/seladin-1 exert antiapoptotic function by conferring resistance against oxidative stress, the molecular mechanism for this protective effect is not fully understood....
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00584-07
更新日期:2008-01-01 00:00:00
abstract::Repetitive DNA sequences have been implicated in the mediation of DNA rearrangement in mammalian cells. We have tested this hypothesis by using a dihydrofolate reductase (DHFR) expression vector into which candidate sequences were inserted. DHFR- Chinese hamster ovary (CHO) cells were transfected with this vector, the...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.8.9.3611
更新日期:1988-09-01 00:00:00
abstract::Multipotential stem cell lines, derived specifically from long-term bone marrow cultures infected with a recombinant retrovirus carrying v-src, lack v-src. Stable consequences thus result from transient actions or indirect effects of v-src on other cells, with the latter possibility being favored by its mosaic express...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.6.3.959
更新日期:1986-03-01 00:00:00
abstract::p27(Kip1) is a member of the Cip-Kip family of cyclin-dependent kinase (Cdk) inhibitors that binds to cyclin-Cdk complexes and inhibits their catalytic activity in response to antiproliferative stimuli. p27(Kip1) is regulated by several posttranscriptional mechanisms, including subcellular localization. We have identi...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.20.15.5631-5642.2000
更新日期:2000-08-01 00:00:00
abstract::To investigate the role of myogenin in regulating acetylcholine receptor expression in adult muscle, this muscle-specific basic helix-loop-helix transcription factor was overexpressed in transgenic mice by using regulatory elements conferring strong expression confined to differentiated postmitotic muscle fibers. Many...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.15.12.7127
更新日期:1995-12-01 00:00:00
abstract::The mechanism by which the maize autonomous Ac transposable element gives rise to nonautonomous Ds elements is largely unknown. Sequence analysis of native maize Ds elements indicates a complex chimeric structure formed through deletions of Ac sequences with or without insertions of Ac-unrelated sequence blocks. These...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.17.11.6294
更新日期:1997-11-01 00:00:00