Abstract:
:Poly(ADP-ribosyl)ation is a post-translational modification of proteins involved in the regulation of chromatin structure, DNA metabolism, cell division and cell death. Through the hydrolysis of poly(ADP-ribose) (PAR), Poly(ADP-ribose) glycohydrolase (PARG) has a crucial role in the control of life-and-death balance following DNA insult. Comprehension of PARG function has been hindered by the existence of many PARG isoforms encoded by a single gene and displaying various subcellular localizations. To gain insight into the function of PARG in response to irradiation, we constitutively and stably knocked down expression of PARG isoforms in HeLa cells. PARG depletion leading to PAR accumulation was not deleterious to undamaged cells and was in fact rather beneficial, because it protected cells from spontaneous single-strand breaks and telomeric abnormalities. By contrast, PARG-deficient cells showed increased radiosensitivity, caused by defects in the repair of single- and double-strand breaks and in mitotic spindle checkpoint, leading to alteration of progression of mitosis. Irradiated PARG-deficient cells displayed centrosome amplification leading to mitotic supernumerary spindle poles, and accumulated aberrant mitotic figures, which induced either polyploidy or cell death by mitotic catastrophe. Our results suggest that PARG could be a novel potential therapeutic target for radiotherapy.
journal_name
J Cell Scijournal_title
Journal of cell scienceauthors
Amé JC,Fouquerel E,Gauthier LR,Biard D,Boussin FD,Dantzer F,de Murcia G,Schreiber Vdoi
10.1242/jcs.039115subject
Has Abstractpub_date
2009-06-15 00:00:00pages
1990-2002issue
Pt 12eissn
0021-9533issn
1477-9137pii
jcs.039115journal_volume
122pub_type
杂志文章abstract::An essential step in mammalian fertilisation is the sperm acrosome reaction (AR) - exocytosis of a single large vesicle (the acrosome) that surrounds the nucleus at the apical sperm head. The acrosomal and plasma membranes fuse, resulting in both the release of factors that might facilitate penetration of the zona pel...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.030379
更新日期:2008-07-01 00:00:00
abstract::The monoclonal antibody AGF2.3 identifies a nuclear envelope protein that is restricted to certain cell types. In particular, this antigen shows a reduced level of expression during haemopoietic cell maturation. In this study, we have examined the relationship of this protein to known nuclear envelope proteins that ha...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1988-06-01 00:00:00
abstract::Trypsin digestion of demembranated fowl spermatozoa caused a longitudinal splitting of the distal part of the axoneme. The resulting strands, consisting of groups of doublet microtubules, formed left-handed helices. On the evidence of electron micrographs, the digestion had caused the loss of dynein arms from the oute...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1987-10-01 00:00:00
abstract::Different isoforms of non-muscle myosin II have different distributions in vivo, even within individual cells. In order to understand how these different distributions arise, the distribution and dynamics of non-muscle myosins IIA and myosin IIB were examined in cultured cells using immunofluorescence staining and tim...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1998-08-01 00:00:00
abstract::Cells that are treated long-term with TNFalpha or short-term with TGFalpha together with cycloheximide (CHX) undergo apoptosis. Cell shrinkage and detachment during apoptosis is dependent on actomyosin contractility. Myosin II heavy chain (MHCII) isoforms have shared and distinct functions. Here, we investigated wheth...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.022640
更新日期:2008-05-15 00:00:00
abstract::During mouse meiosis, the early prophase RAD51/DMC1 recombination protein sites, which are associated with the chromosome cores and which serve as markers for ongoing DNA-DNA interactions, are in ten-fold excess of the eventual reciprocal recombinant events. Most, if not all, of these early interactions are eliminated...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:2002-04-15 00:00:00
abstract::In order to replicate, most pathogens need to enter their target cells. Many viruses enter the host cell through an endocytic pathway and hijack endosomes for their journey towards sites of replication. For delivery of their genome to the host cell cytoplasm and to avoid degradation, viruses have to escape this endoso...
journal_title:Journal of cell science
pub_type: 杂志文章,评审
doi:10.1242/jcs.216259
更新日期:2018-08-03 00:00:00
abstract::Expression of actin was examined in a cultured rat embryonic cell line 3Y1 and transformed cell lines that originated from 3Y1. An alpha-actin in addition to cytoplasmic beta- and gamma-actins was detected in 3Y1 by two-dimensional gel electrophoresis. This alpha-actin was hardly detected at all in the transformants i...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1990-08-01 00:00:00
abstract::The events that accompany sporogenesis in the apogamous fern Dryopteris borreri parallel those seen in sexually reproducing ferns. Organelles dedifferentiate and redifferentiate, and form a discrete band across the equator of dyads; nuclear vacuoles and lipid spherosomes appear during prophase, and the major part of t...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1983-09-01 00:00:00
abstract::Activator of G-protein signaling 3 (AGS3, also known as GPSM1) regulates the trans-Golgi network. The AGS3 GoLoco motif binds to Gαi and thereby regulates the transport of proteins to the plasma membrane. Compaction of early embryos is based on the accumulation of E-cadherin (Cdh1) at cell-contacted membranes. However...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.243238
更新日期:2020-12-07 00:00:00
abstract::Transforming growth factor beta (TGFbeta) plays an important role in development and maintenance of murine yolk sac vascular development. Targeted deletions of Tgfb1 and other components of this signaling pathway, such as Acvrl1, Tgfbr1 and Tgfbr2, result in abnormal vascular development especially of the yolk sac, le...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.02788
更新日期:2006-02-15 00:00:00
abstract::The regulation of mitochondrial dynamics by the GTPase OPA1, which is located at the inner mitochondrial membrane, is crucial for adapting mitochondrial function and preserving cellular health. OPA1 governs the delicate balance between fusion and fission in the dynamic mitochondrial network. A disturbance of this bala...
journal_title:Journal of cell science
pub_type: 杂志文章,评审
doi:10.1242/jcs.159186
更新日期:2016-06-15 00:00:00
abstract::The cell surface delivery of extracellular matrix (ECM) and integrins is fundamental for cell migration in wound healing and during cancer cell metastasis. This process is not only driven by several soluble NSF attachment protein (SNAP) receptor (SNARE) proteins, which are key players in vesicle transport at the cell ...
journal_title:Journal of cell science
pub_type: 杂志文章,评审
doi:10.1242/jcs.164459
更新日期:2015-03-15 00:00:00
abstract::Eukaryotic gene expression can be viewed within a conceptual framework in which regulatory mechanisms are integrated at three hierarchical levels. The first is the sequence level, i.e. the linear organization of transcription units and regulatory sequences. Here, developmentally co-regulated genes seem to be organized...
journal_title:Journal of cell science
pub_type: 杂志文章,评审
doi:10.1242/jcs.00779
更新日期:2003-10-15 00:00:00
abstract::Targeting of the NG2 proteoglycan to cellular retraction fibers was studied by expressing mutant NG2 molecules lacking specific structural elements of the proteoglycan. Both the cytoplasmic domain and the chondroitin sulfate chain of NG2 appear to have roles in sorting NG2 to subcellular microdomains destined to becom...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:2001-06-01 00:00:00
abstract::Actin filaments assemble into diverse protrusive and contractile structures to provide force for a number of vital cellular processes. Stress fibers are contractile actomyosin bundles found in many cultured non-muscle cells, where they have a central role in cell adhesion and morphogenesis. Focal-adhesion-anchored str...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.098087
更新日期:2012-04-15 00:00:00
abstract::During the first meiotic prophase, alignment and synapsis of the homologous chromosomes are mediated by the synaptonemal complex. Incorrect assembly of this complex results in cell death, impaired meiotic recombination and formation of aneuploid germ cells. We have identified a novel mouse meiosis-specific protein, TE...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.03182
更新日期:2006-10-01 00:00:00
abstract::It remains unclear how GPI-anchored proteins (GPIAPs), which lack cytoplasmic domains, transduce signals triggered by specific ligation. Such signal transduction has been speculated to require the ligated GPIAP to associate with membrane-spanning proteins that communicate with obligate cytoplasmic proteins. Transient ...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.049346
更新日期:2009-11-01 00:00:00
abstract::Human peripheral blood eosinophils attach to and flatten down onto antibody-coated surfaces and subsequently degranulate. An antibody-coated surface was prepared by treating a layer of agar, containing tetanus toxoid antigen and eosinophil chemotactic factor (ECF), with human anti-tetanus immunoglobin. Changes in eosi...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1982-08-01 00:00:00
abstract::Shape changes have been determined in human blood lymphocytes stimulated with OAG, diC8, PMA, colchicine or the hexapeptide fNLPNTL in short-term assays (30 min). Distinct types of shape-change responses were observed. Colchicine was active in generating a relatively small proportion of polarized lymphocytes (front-ta...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1989-07-01 00:00:00
abstract::Rac1 is a small Rho family GTPase that regulates changes in cell morphology associated with cell spreading and migration. Integrin-mediated adhesion is known to activate Rac1 and to regulate the interaction of Rac1 with downstream effectors. Currently, it is not clear how integrins signal Rac1 activation following cel...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.00109
更新日期:2002-11-15 00:00:00
abstract::The SPN antigen plays an essential role in mitosis, since microinjection of antibodies causes mitotic arrest. Here we show, by examination of the relative locations of SPN antigen, the centrosomal 5051 antigen and tubulin in normal mitotic, and in taxol-treated mitotic cells, that the SPN antigen is involved in organi...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1992-05-01 00:00:00
abstract::We have explored the biological function of a surface glycoprotein (GP72) of Trypanosoma cruzi by studying a null mutant parasite, generated by targeted gene deletion. GP72 deletion affected parasite morphology in several stages of the life cycle. Insect midgut (epimastigote) forms had a detached flagellum (apomastigo...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1993-12-01 00:00:00
abstract::Immunofluorescent anti-tubulin staining has been used to follow nuclear progression from dictyate to metaphase II during meiotic maturation of mouse oocytes in vitro. Antibody directed against tubulin isolated from sea-urchin eggs decorates the metaphase I and metaphase II spindles, as well as the cytoplasmic bridge, ...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1978-02-01 00:00:00
abstract::The extracellular environment and tissue architecture contribute to proper cell function and growth control. Cells growing in monolayers on standard polystyrene tissue culture plates differ in their shape, growth rate and response to external stimuli, compared with cells growing in vivo. Here, we showed that the EGFR ...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.054551
更新日期:2009-12-01 00:00:00
abstract::Organelle transport is vital for the development and maintenance of axons, in which the distances between sites of organelle biogenesis, function, and recycling or degradation can be vast. Movement of mitochondria in axons can serve as a general model for how all organelles move: mitochondria are easy to identify, the...
journal_title:Journal of cell science
pub_type: 杂志文章,评审
doi:10.1242/jcs.02745
更新日期:2005-12-01 00:00:00
abstract::Histone proteins are essential for chromatin formation, and histone gene expression is coupled to DNA synthesis. In metazoans, the histone RNA binding protein HBP/SLBP is involved in post-transcriptional control of histone gene expression. In vitro assays have demonstrated that human HBP/SLBP is involved in histone mR...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.01523
更新日期:2004-12-01 00:00:00
abstract::The identification and characterization of scaffold and targeting proteins of the ERK/MAP kinase pathway is important to understand the function and intracellular organization of this pathway. The F-actin binding protein leukocyte-specific protein 1 (LSP1) binds to PKCbetaI and expression of B-LSP1, an LSP1 truncate c...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.00955
更新日期:2004-04-15 00:00:00
abstract::Centriolar satellites are membrane-less structures that localize and move around the centrosome and cilium complex in a microtubule-dependent manner. They play important roles in centrosome- and cilium-related processes, including protein trafficking to the centrosome and cilium complex, and ciliogenesis, and they are...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.196832
更新日期:2017-04-15 00:00:00
abstract::Endothelial cells are known to undergo transitions in cell shape during long-term culture. Thus, the assumption that the separate phenotypes of microvascular endothelial cells (MVEC) recently isolated from bovine corpus luteum represent constitutively different cell strains cannot automatically be made. For this reaso...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1993-11-01 00:00:00