scholarly journals Muscle tensions merge to cause a DNA replication crisis

2018 ◽  
Vol 217 (6) ◽  
pp. 1891-1893 ◽  
Author(s):  
Daniel Brayson ◽  
Chin Yee Ho ◽  
Catherine M. Shanahan
Keyword(s):  
Dna Replication ◽  
Muscle Cells ◽  
Epigenetic Mechanisms ◽  
Cell Biol ◽  
Replication Crisis ◽  
Dna Endoreplication

In this issue, Wang et al. (2018. J. Cell Biol. https://doi.org/10.1083/jcb.201708137) show that disruption to different mechanical domains of muscle cells converge at the linker of nucleoskeleton to cytoskeleton complex to affect DNA endoreplication potentially via barrier to autointegration factor–mediated epigenetic mechanisms.

scholarly journals Dynamics of sister chromatids through the cell cycle: Together and apart

2018 ◽  
Vol 217 (6) ◽  
pp. 1887-1889 ◽  
Author(s):  
Motoko Takahashi ◽  
Toru Hirota
Keyword(s):  
Cell Cycle ◽  
Dna Replication ◽  
Sister Chromatid ◽  
Fundamental Question ◽  
Live Cells ◽  
Sister Chromatids ◽  
Cell Biol

When and how sister chromatid resolution occurs after DNA replication is a fundamental question. Stanyte et al. (2018. J. Cell Biol. https://doi.org/10.1083/jcb.201801157) used CRISPR/Cas9 technology to label and track genomic loci in live cells throughout the cell cycle, shedding light on how replication is linked to mitotic sister chromatid organization.

scholarly journals Deoxyribonucleic acid methylation and chromatin organization in Tetrahymena thermophila.

1981 ◽  
Vol 1 (7) ◽  
pp. 600-608 ◽  
Author(s):  
K Pratt ◽  
S Hattman
Keyword(s):  
Dna Replication ◽  
Dna Sequence ◽  
Dna Sequences ◽  
Cytosine Methylation ◽  
Deoxyribonucleic Acid ◽  
Tetrahymena Thermophila ◽  
Staphylococcal Nuclease ◽  
Chromatin Organization ◽  
Deoxyribonuclease I ◽  
Cell Biol

Deoxyribonucleic acid (DNA) of the transcriptionally active macronucleus of Tetrahymena thermophila is methylated at the N6 position of adenine to produce methyladenine (MeAde); approximately 1 in every 125 adenine residues (0.8 mol%) is methylated. Transcriptionally inert micronuclear DNA is not methylated (< or = 0.01 mol% MeAde; M. A. Gorovsky, S. Hattman, and G. L. Pleger, J. Cell Biol. 56:697-701, 1973). There is no detectable cytosine methylation in macronuclei in Tetrahymena DNA (< or = 0.01 mol% 5-methylcytosine). MeAde-containing DNA sequences in macronuclei are preferentially digested by both staphylococcal nuclease and pancreatic deoxyribonuclease I. In contrast, there is no preferential release of MeAde during digestion of purified DNA. These results indicate that MeAde residues are predominantly located in "linker DNA" and perhaps have a function in transcription. Pulse-chase studies showed that labeled MeAde remains preferentially in linker DNA during subsequent rounds of DNA replication; i.e., there is little, if any, movement of nucleosomes during chromatin replication. This implies that nucleosomes may be phased with respect to DNA sequence.

REGULATION OF GROWTH FACTOR PRODUCTION BY ENDOTHELIAL CELLS IN RESPONSE TO COAGULATION AND INFLAMATORY FACTORS

1987 ◽  
Author(s):  
D F Bowen-Pope ◽  
C Gajdusek ◽  
J Harlan ◽  
P Nawroth ◽  
R Ross ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Growth Factor ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Atherosclerotic Lesions ◽  
Cell Biol ◽  
Stimulation Of

Platelet-derived growth factor (PDGF) is a polypeptide growth factor first discovered in, and purified from, human blood platelets. As assayed by its ability to stimulate proliferation of cultured vascular smooth muscle cells, PDGF is the major mitogen in human whole blood serum. PDGF has also been reported to be chemotactic for fibroblasts, vascular smooth muscle cells, and leukocytes, and to be able to stimulate contraction of arterial smooth muscle. This, spectrum of activities suggests that PDGF could play a significant role in several vascular processes, including wound repair and the formation of atherosclerotic lesions (reviewed in Ross et al., 1986 Cell 46:155). Several cell types in addition to the platelet have now been shown to be capable of secreting PDGF-like molecules. In culture, vascular endothelial cells from many sources secrete significant levels of PDGF (DiCorleto and Bowen-Pope, 1983 PNAS 80:1919). Rates of secretion can be increased four fold and more bythe activated procoagulants thrombin (Harlan et al 1986 J. Cell Biol. 103:1129) and factor Xa (Gajdusek et al 1986 J. Cell Biol. 103:419). Thrombin stimulates secretion by the earliest times measurable (about 1.5hr) and this early response is not diminished by inhibitors of protein and RNA synthesis. Nevertheless, unlike secretion from the platelet, stimulated secretion does not represent release of sequestered active PDGF since no reservoir of active PDGF can be detected within the cells prior to stimulation. It is likely therefore that stimulation of secrtion involves the activation or unmasking of an inactive form of PDGF. The proteolytic activities of thrombin and Xa are necessary for activation of secretion but the mechanism does not seem to to involve direct proteolytic activation by thrombin of a precursor since thrombin treatment does not generate active PDGF in freeze-thawed preparations of endothelial cells. We have recently found that tumor necrosis factor alpha (TNF) and gamma interferon (IFN) can stimulate increased rates of secretion of PDGF by cultured human saphenous vein and umbilical vein endothelial cells. Stimulation by a combination of the two is more than additive. In contrast to the rapid kinetics of stimulation by thrombin and Xa, TNF and IFN do not measurably increase secretion for at lease four hrs. This delayed kinetics is paralleled by increases in mRNA encoding the two subunit chains of PDGF ("A" and "B") and it seems likely that in this case stimulation of secretion results from increased rates of mRNA and protein synthesis. Since evidence is accumulating that TNF and IFN are both present in human atherosclerotic lesions, it is possible that they help stimulate production of endothelial cell-derived mitogens, including PDGF and thus contribute to the development of the lesion.

scholarly journals Beginning at the end: DNA replication within the telomere

2015 ◽  
Vol 210 (2) ◽  
pp. 177-179 ◽  
Author(s):  
Susan A. Gerbi
Keyword(s):  
Dna Replication ◽  
Mouse Chromosome ◽  
Single Molecule ◽  
Template Strand ◽  
Cell Biol ◽  
Chromosome Arm ◽  
Leading Strand ◽  
Wrn Helicase ◽  
Single Molecule Analysis

Using single molecule analysis of replicated DNA (SMARD), Drosopoulos et al. (2015; J. Cell Biol. http://dx.doi.org/10.1083/jcb.201410061) report that DNA replication initiates at measurable frequency within the telomere of mouse chromosome arm 14q. They demonstrate that resolution of G4 structures on the G-rich template strand of the telomere requires some overlapping functions of BLM and WRN helicase for leading strand synthesis.

Identification of multiple proteins that interact with functional regions of the human cardiac alpha-actin promoter

1989 ◽  
Vol 9 (8) ◽  
pp. 3269-3283
Author(s):  
T A Gustafson ◽  
L Kedes
Keyword(s):  
Transcription Factor ◽  
Muscle Cells ◽  
Tata Box ◽  
Actin Gene ◽  
Functional Importance ◽  
Cell Biol ◽  
Proximal Site ◽  
Gel Shift ◽  
A Site ◽  
Alpha Actin

5' Sequences of the human cardiac alpha-actin gene are involved in the tissue-specific and developmental regulation of the gene. Deletion analyses combined with transient expression experiments in muscle cells have demonstrated three primary regions of functional importance (A. Minty and L. Kedes, Mol. Cell. Biol. 6:2125-2136, 1986; T. Miwa and L. Kedes, Mol. Cell. Biol. 7:2803-2813, 1987), and we have previously demonstrated binding of a protein indistinguishable from serum response factor (SRF) to the most proximal region (T.A. Gustafson, T. Miwa, L.M. Boxer, and L. Kedes, Mol. Cell. Biol. 8:4110-4119, 1988). In this report, we examine protein interaction with the remainder of the promoter. Gel shift and footprinting assays revealed that at least seven distinct nuclear proteins interacted with known and putative regulatory regions of the promoter. The transcription factor Sp1 bound to eight sites, as demonstrated by footprinting assays and gel shift analysis with purified Sp1. Purified CCAAT box-binding transcription factor CTF/NF-I and Sp1 were shown to interact with the far-upstream regulatory element at -410, and footprint analysis showed extensive overlap of these two sites. Two unidentified proteins with similar but distinct footprints interacted with the second region of functional importance at -140, which contains the second CArG motif [CC(A + T rich)6GG], and these proteins were shown to be distinct from SRF. SRF was found to bind to the remaining three CArG boxes, two of which were closely interdigitated with Sp1 sites. In addition, CArG box 4 was found to interact with SRF and another distinct protein whose footprint was contained within the SRF-binding site. Sequences surrounding the TATA box were also shown to bind proteins. Sp1 was shown to bind to a site immediately downstream from the TATA box and to a site within the first exon. Thus, each of the three functional upstream regions, as defined by transfection assays, was shown to interact with five factors: Sp1 and CTF/NF-I at the upstream site, two unidentified proteins at the central site, and SRF at the most proximal site. These results suggest that expression of the cardiac actin gene in muscle cells is controlled by complex interactions among multiple upstream and intragenic elements.

On the mechanism of induction of DNA synthesis in cultured arterial smooth muscle cells by leukotrienes. Possible role of prostaglandin endoperoxide synthase products and platelet-derived growth factor

1991 ◽  
Vol 98 (2) ◽  
pp. 141-149
Author(s):  
L. Palmberg ◽  
J.A. Lindgren ◽  
J. Thyberg ◽  
H.E. Claesson
Keyword(s):  
Arachidonic Acid ◽  
Smooth Muscle ◽  
Dna Replication ◽  
Growth Factor ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Platelet Derived Growth Factor ◽  
Specific Cell ◽  
Prostaglandin Endoperoxide ◽  
Prostaglandin Endoperoxide Synthase

The induction of DNA replication in rat aortic smooth muscle cells (SMCs) by leukotrienes (LTs) was studied in order to elucidate the mechanisms of action in further detail. The effect of LTB4 was blocked by the prostaglandin (PG) synthesis inhibitor indomethacin and the effects of LTC4 and LTD4 were blocked by the cysteinyl-containing leukotriene receptor antagonists FPL 55712 and ICI 198615. These observations suggest that LTB4 and the cysteinyl-containing leukotrienes act via distinct receptors and point to a role for prostaglandin endoperoxide synthase products in bringing about the effect of LTB4. Radioimmunological determinations and analyses of [3H]arachidonic acid metabolism showed that the SMCs were able to synthesize PGI2 (measured as the stable metabolite 6-keto-PGF1 alpha), PGE2, PGF2 alpha and 15(S)hydroxy-eicosatetraenoic acid (15(S)HETE). Moreover, picomolar concentrations of arachidonic acid, PGI2, PGE2, PGF2 alpha and 15(S)HETE induced DNA replication in the SMCs under serum-free conditions, whereas linoleic acid, 6-keto-PGF1 alpha and 5(S)HETE were inactive in this respect. Analysis of conditioned media for mitogenic activity (with or without antibodies against platelet-derived growth factor, PDGF) and for the presence of material competing with radioiodinated PDGF for binding to specific cell surface receptors indicated that LTB4 stimulated release of PDGF or a PDGF-like molecule from the cells. These findings suggest that the growth-promoting effect of LTB4 is mediated via a prostaglandin endoperoxide synthase product and/or PDGF produced by the cells themselves.

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