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Nuclear Matrix (nuclear + matrix)
Terms modified by Nuclear Matrix Selected AbstractsThe sperm nuclear matrix is required for paternal DNA replication,JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 3 2007Jeffrey A. Shaman Abstract The mammalian sperm nucleus provides an excellent model for studying the relationship between the formation of nuclear structure and the initiation of DNA replication. We previously demonstrated that mammalian sperm nuclei contain a nuclear matrix that organizes the DNA into loop domains in a manner similar to that of somatic cells. In this study, we tested the minimal components of the sperm nucleus that are necessary for the formation of the male pronucleus and for the initiation of DNA synthesis. We extracted mouse sperm nuclei with high salt and dithiothreitol to remove the protamines in order to form nuclear halos. These were then treated with either restriction endonucleases to release the DNA not directly associated with the nuclear matrix or with DNAse I to digest all the DNA. The treated sperm nuclei were injected into oocytes, and the paternal pronuclear formation and DNA synthesis was monitored. We found that restriction digested sperm nuclear halos were capable of forming paternal pronuclei and initiating DNA synthesis. However, when isolated mouse sperm DNA or sperm DNA reconstituted with the nuclear matrices were injected into oocytes, no paternal pronuclear formation or DNA synthesis was observed. These data suggest that the in situ nuclear matrix attachment organization of sperm DNA is required for mouse paternal pronuclear DNA synthesis. J. Cell. Biochem. 102: 680,688, 2007. © 2007 Wiley-Liss, Inc. [source] Cancer-associated missplicing of exon 4 influences the subnuclear distribution of the DNA replication factor CIZ1,HUMAN MUTATION, Issue 10 2007Faisal Abdel Rahman Abstract Cip1-interacting zinc finger protein 1 (CIZ1, also known as CDKN1A-interacting zinc finger protein 1) stimulates initiation of mammalian DNA replication and is normally tethered to the nuclear matrix within DNA replication foci. Here, we show that an alternatively spliced human CIZ1 variant, lacking exon 4 (, E4), is misexpressed as a consequence of intronic mutation in Ewing tumor (ET) cell lines. In all ET lines tested, exon 4 is skipped and an upstream mononucleotide repeat element is expanded to contain up to 28 thymidines, compared to 16 in controls. In exon-trap experiments, a 24T variant produced three-fold more exon skipping than a 16T variant, demonstrating a direct effect on splicing. In functional assays, , E4 protein retains replication activity, but fails to form subnuclear foci. Furthermore, coexpression of mouse , E4 with Ciz1 prevents Ciz1 from localizing appropriately, having a dominant negative effect on foci formation. The data show that conditional exclusion of exon 4 influences the spatial distribution of the Ciz1 protein within the nucleus, and raise the possibility that CIZ1 alternative splicing could influence organized patterns of DNA replication. Hum Mutat 28(10), 993,1004, 2007. © 2007 Wiley-Liss, Inc. [source] Lipid,nucleic acids interactions as base for organization and expression of cellular genomeINTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY, Issue 1 2010V. V. Kuvichkin Abstract Although lipid,nucleic acid interactions have been studied, with certain or little progress, for more than 30 years, it is only in recent years that the problem has received particular attention. It should, however, be noted that most studies deal with DNA-cationic surfactants interactions, whereas DNA-zwitterionic interactions, which are more complex and close to nature, are poorly investigated. The long-standing studies of the triple complexes: DNA,phosphatidylcholine liposomes,divalent metal cations allow us to confirm that these complexes are responsible for the formation of not only the structures existing in DNA,cationic liposome complexes but also some other cellular structures. The author proposed hypothesis about the involvement of direct DNA,lipid interactions in the nuclear pore assembly. Only taking into account interactions between DNA and lipids of cellular membrane, one can explain the origin of such structures as nucleoid, nuclear pore, and nuclear matrix. The formation of triple complexes was accompanied by the aggregation and partial fusion of liposomes as was shown by cryo-TEM technique. The author has presented new data on the structure of triple complexes, which were obtained by phase contrast cryo-TEM. Biophysical data on the liposomes fusion during triple complex formation and perspective of their computer simulation are also presented. DNA acts as a fusogen in this process and it unwinds in the region of liposomes fusion. The nuclear envelope and pore complexes assembly is provided by membrane vesicles fusion. Author has proposed that the DNA-induced fusion of zwitterionic liposomes in vitro may suggest the involvement of direct lipids,DNA interaction in nuclear envelope assembly. © 2009 Wiley Periodicals, Inc. Int J Quantum Chem, 2010 [source] Localization of nucleophosmin in nuclear matrix and changes in its expression during the differentiation of human neuroblastoma induced by retinoic acid,JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 1 2010Song-Lin Shi Abstract In this article, we selectively extracted the nuclear matrix and intermediate filament system of human neuroblastoma SK-N-SH cells pre- and post-treated with retinoic acid (RA). The distribution of nucleophosmin (NPM) in the nuclear matrix and its colocalization with several products of related genes were investigated. Results from two-dimensional gel electrophoresis and MALDI-TOF showed that NPM was a component of the nuclear matrix and its expression in SK-N-SH cells post-treated with RA was down-regulated. Immunofluorescent microscopy observations further showed that NPM was localized in the nuclear matrix of SK-N-SH cells, and its expression level and distribution were altered after treatment with RA. The colocalization of NPM with c-myc, c-fos, p53, and Rb in SK-N-SH cells was observed under a laser scanning confocal microscope, but the colocalization region was changed by RA. Our results prove that NPM is a nuclear matrix protein, which is localized in nuclear matrix fibers. The colocalization of NPM with its related genes and oncogenes affect the differentiation of SK-N-SH cells. The expression of NPM and its distribution in the process of cell differentiation deserve more intensive investigation. J. Cell. Biochem. 111: 67,74, 2010. © 2010 Wiley-Liss, Inc. [source] The sperm nuclear matrix is required for paternal DNA replication,JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 3 2007Jeffrey A. Shaman Abstract The mammalian sperm nucleus provides an excellent model for studying the relationship between the formation of nuclear structure and the initiation of DNA replication. We previously demonstrated that mammalian sperm nuclei contain a nuclear matrix that organizes the DNA into loop domains in a manner similar to that of somatic cells. In this study, we tested the minimal components of the sperm nucleus that are necessary for the formation of the male pronucleus and for the initiation of DNA synthesis. We extracted mouse sperm nuclei with high salt and dithiothreitol to remove the protamines in order to form nuclear halos. These were then treated with either restriction endonucleases to release the DNA not directly associated with the nuclear matrix or with DNAse I to digest all the DNA. The treated sperm nuclei were injected into oocytes, and the paternal pronuclear formation and DNA synthesis was monitored. We found that restriction digested sperm nuclear halos were capable of forming paternal pronuclei and initiating DNA synthesis. However, when isolated mouse sperm DNA or sperm DNA reconstituted with the nuclear matrices were injected into oocytes, no paternal pronuclear formation or DNA synthesis was observed. These data suggest that the in situ nuclear matrix attachment organization of sperm DNA is required for mouse paternal pronuclear DNA synthesis. J. Cell. Biochem. 102: 680,688, 2007. © 2007 Wiley-Liss, Inc. [source] Gene positional changes relative to the nuclear substructure during carbon tetrachloride-induced hepatic fibrosis in ratsJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 6 2004Apolinar Maya-Mendoza Abstract In the interphase nucleus the DNA of higher eukaryotes is organized in loops anchored to a substructure known as the nuclear matrix (NM). The topological relationship between gene sequences located in the DNA loops and the NM appears to be very important for nuclear physiology because processes such as replication, transcription, and processing of primary transcripts occur at macromolecular complexes located at discrete sites upon the NM. Mammalian hepatocytes rarely divide but preserve a proliferating capacity that is displayed in vivo after specific stimulus. We have previously shown that transient changes in the relative position of specific genes to the NM occur during the process of liver regeneration after partial ablation of the liver, but also that such changes correlate with the replicating status of the cells. Moreover, since chronic exposure to carbon tetrachloride (CCl4) leads to bouts of hepatocyte damage and regeneration, and eventually to non-reversible liver fibrosis in the rat, we used this animal model in order to explore if genes that show differential activity in the liver change or modify their relative position to the NM during the process of liver fibrosis induction. We found that changes in the relative position of specific genes to the NM occur during the chronic administration of CCl4, but also that such changes correlate with the proliferating status of the hepatocytes that goes from quiescence to regeneration to replicative senescence along the course of CCl4 -induced liver fibrosis, indicating that specific configurations in the higher-order DNA structure underlie the stages of progression towards liver fibrosis. © 2004 Wiley-Liss, Inc. [source] Alterations in intranuclear localization of Runx2 affect biological activity,,JOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2006Sayyed K. Zaidi The transcription factor Runx2 controls osteoblast proliferation and differentiation. Runx2 organizes and assembles gene-regulatory complexes in nuclear microenvironments where target genes are activated or suppressed in a context-dependent manner. Intranuclear localization of Runx2 is mediated by the nuclear matrix-targeting signal (NMTS), an autonomous motif with a loop (L1)-turn-loop (L2) structure that forms predicted protein,protein interaction surfaces. Here we examined the functional consequences of introducing mutations in the L1 and L2 loops of the NMTS. These mutant proteins enter the nucleus, interact with the hetero-dimeric partner Cbf,, and bind to DNA in vitro and in vivo. In addition, these mutants retain interaction with the carboxy-terminus interacting co-regulatory proteins that include TLE, YAP, and Smads. However, two critical mutations in the L2 domain of the NMTS decrease association of Runx2 with the nuclear matrix. These subnuclear targeting defective (STD) mutants of Runx2 compromise target gene activation or repression. The biological significance of these findings is reflected by decreased osteogenic differentiation of mesenchymal progenitors, concomitant with major changes in gene expression profiles, upon expression of the STD Runx2 mutant. Our results demonstrate that fidelity of temporal and spatial localization of Runx2 within the nucleus is functionally linked with biological activity. J. Cell. Physiol. 209: 935,942, 2006. © 2006 Wiley-Liss, Inc. [source] A comparison of urinary nuclear matrix protein-22 and bladder tumour antigen tests with voided urinary cytology in detecting and following bladder cancer:the prognostic value of false-positive resultsBJU INTERNATIONAL, Issue 7 2001V. Poulakis Objectives To evaluate the diagnostic and prognostic value of the nuclear matrix protein-22 (NMP22) and bladder tumour antigen (BTAstat) tests compared with voided urinary cytology (VUC) in detecting and following bladder cancer, assessing particularly the prognostic value of false-positive test results in patients followed up for bladder cancer. Patients and methods From 739 patients suspected of having bladder cancer, voided urine samples for the NMP22 and BTAstat tests, and for VUC and urine analysis, were collected before cystoscopy. All patients underwent transurethral resection of bladder lesions or mapping, and were followed for a mean (range) of 27.3 (3,65) months. Results In the 406 patients with bladder cancer, the overall sensitivity was 85% for NMP22, 70% for BTAstat and 62% for VUC. For histological grades 1,3 the sensitivity in detecting transitional cell carcinoma was 82%, 89% and 94% for NMP22, 53%, 76% and 90% for BTAstat, and 38%, 68% and 90% for VUC, respectively. Although the sensitivity in detecting invasive carcinoma was > 85% for all the tests, NMP22 and BTAstat were statistically more sensitive than VUC for superficial tumours. The optimal threshold value for NMP22, calculated using the receiver operating characteristics curve, was 8.25 U/mL. The specificity was 68% for NMP22, 67% for BTAstat, and 96% for VUC. The specificity of VUC remained > 87% and was independent of benign histological findings. In contrast, in patients with no apparent genitourinary disease on histology, NMP22 and BTAstat had significantly higher specificity (94% and 92%, respectively; P = 0.003) than in the group with chronic cystitis (52% for both tests). Forty patients having no bladder cancer at biopsy had a recurrence after a mean (range) follow-up of 7.7 (3,15) months; all had a previous history of bladder cancer. According to subsequent recurrence, the prognostic positive and negative predictive values were 18% and 91% for NMP22, 13% and 88% for BTAstat, and 79% and 91% for VUC. Both false-positive VUC and NMP22 tests predicted recurrence (log-rank test, P < 0.001 and P = 0.004, respectively), but the BTAstat test produced no similar correlation (P = 0.778). Conclusion The NMP22 and BTAstat tests are better than VUC for detecting superficial and low-grade bladder cancer but they have significantly lower specificity. After excluding diseases with the potential to interfere in these tests the overall specificity of both tests is increased considerably. False-positive results from NMP22 and VUC but not from BTAstat in patients followed up for bladder cancer correlate with future recurrences. [source] |