scholarly journals Histone synthesis in Leishmania infantum is tightly linked to DNA replication by a translational control

2000 ◽  
Vol 346 (1) ◽  
pp. 99-105 ◽  
Author(s):  
Manuel SOTO ◽  
Luis QUIJADA ◽  
Carlos ALONSO ◽  
Jose M. REQUENA

We have analysed the regulation of histone synthesis in Leishmania infantum following inhibition of DNA replication. Run-on experiments indicated that transcription rates of the genes coding for the four core histones (H2A, H2B, H3 and H4) were not affected by the inhibition with hydroxyurea of DNA synthesis. However, a dramatic decrease was observed in the newly synthesized histones after inhibition of DNA synthesis. Furthermore, the synthesis of both the histones and DNA resumed in promastigotes after removal of hydroxyurea, indicating that inhibition was reversible. Unlike most eukaryotes, in which the replication-dependent histone transcripts decrease upon a replication blockade, the levels of L. infantum histone mRNAs do not change under similar conditions. Thus the present data indicate that histone synthesis in Leishmania is tightly coupled to DNA replication by a mechanism operating at the translational level.

2000 ◽  
Vol 346 (1) ◽  
pp. 99 ◽  
Author(s):  
Manuel SOTO ◽  
Luis QUIJADA ◽  
Carlos ALONSO ◽  
Jose M. REQUENA

2014 ◽  
Vol 50 (3) ◽  
pp. 367-380 ◽  
Author(s):  
Elżbieta Bednarska

DNA and histone synthesis in five consecutive morphological stages of <em>Hyacinthus orientalis</em> L. pollen grain differentiation were studied autoradiographically. DNA synthesis was found to occur in both the generative and the vegetative cell. DNA replication in the generative cell took place when the generative cell was still adhered to the pollen grain wall but already devoid of callose wall. DNA synthesis in the generative cell slightly preceded that in the vegetative cell. Histones were synthesized in phase S of the generative and vegetative cell. In the generative cell histone synthesis also continued at a lower level after completion of DNA replication. In the developmental stages under study the nuclei of the generative cells were decidedly richer in lysine histones than vegetative cell nuclei.


Biochemistry ◽  
1978 ◽  
Vol 17 (23) ◽  
pp. 4885-4893 ◽  
Author(s):  
Paul Nadeau ◽  
Denis R. Oliver ◽  
Roger Chalkley

1980 ◽  
Vol 58 (12) ◽  
pp. 1359-1369 ◽  
Author(s):  
Rose Sheinin ◽  
G. Setterfield ◽  
I. Dardick ◽  
G. Kiss ◽  
M. Dubsky

Mouse L-cells treated with cytosine arabinoside, hydroxyurea, fluorodeoxyuridine, methotrexate, or mitomycin C rapidly cease DNA synthesis and stop dividing. Such inhibition of DNA replication is followed by interruption of formation of lysine- and arginine-containing proteins, including chromatin-bound histones, and by a major reorganization of the heterochromatin of the central nucleoplasm, manifest as disaggregation of large clumps of this condensed chromatin. Morphometric analysis revealed both cell and nuclear enlargement in cells treated with such antimetabolites of DNA replication. These observations are in contrast to those made with WT-4 cells starved of isoleucine or treated with cycloheximide. Isoleucine depletion was associated with inhibition of DNA synthesis and continued increase of cell and nuclear volume, but not with massive disaggregation of heterochromatin. Cycloheximide produced inhibition of DNA synthesis and protoplasmic growth, and also prevented structural reorganization of chromatin. A model is presented which suggests that initiation of chromatin replication is associated with a process, dependent upon de novo protein synthesis, which results in chromatin disaggregation. This can be revealed by inhibition of the correct replication of chromatin DNA and chromatin protein.


Zygote ◽  
1997 ◽  
Vol 5 (2) ◽  
pp. 153-175 ◽  
Author(s):  
Richard Ikegami ◽  
Alma K. Rivera-Bennetts ◽  
Deborah L. Brooker ◽  
Thomas D. Yager

SummaryWe address the developmental activation, in the zebrafish embryo, of intrinsic cell-cycle checkpoints which monitor the DNA replication process and progression through the cell cycle. Eukaryotic DNA replication is probably carried out by a multiprotein complex containing numerous enzymes and accessory factors that act in concert to effect processive DNA synthesis (Applegren, N. et al. (1995) J. Cell. Biochem. 59, 91–107). We have exposed early zebrafish embryos to three chemical agents which are predicted to specifically inhibit the DNA polymerase α, topoisomerase I and topoisomerase II components of the DNA replication complex. We present four findings: (1) Before mid-blastula transition (MBT) an inhibition of DNA synthesis does not block cells from attempting to proceed through mitosis, implying the lack of functional checkpoints. (2) After MBT, the embryo displays two distinct modes of intrinsic checkpoint operation. One mode is a rapid and complete stop of cell division, and the other is an ‘adaptive’ response in which the cell cycle continues to operate, perhaps in a ‘repair’ mode, to generate daughter nuclei with few visible defects. (3) The embryo does not display a maximal capability for the ‘adaptive’ response until several hours after MBT, which is consistent with a slow rranscriptional control mechanism for checkpoint activation. (4) The slow activation of checkpoints at MBT provides a window of time during which inhibitors of DNA synthesis will induce cytogenetic lesions without killing the embryo. This could be useful in the design of a deletion-mutagenesis strategy.


1965 ◽  
Vol 6 (3) ◽  
pp. 479-483 ◽  
Author(s):  
Susan Hollom ◽  
R. H. Pritchard

From studies involving inhibition of DNA synthesis in Hfr strains ofEscherichia coliK12, either by thymine starvation (Pritchard, 1963) or amino-acid starvation (Suit, Matney, Doudney & Billen, 1964), during mating withF−strains, it has been concluded that transfer of DNA from males to females can occur in the absence of DNA synthesis. This conclusion is at variance with the hypothesis (Jacob, Brenner & Cuzin, 1963) that the energy required for transfer is derived from the process of DNA replication. On the other hand, a second prediction from this hypothesis, that one polynucleotide chain of the DNA transferred during mating will have been synthesized during transfer, is strongly supported by recent experiments (Ptashne, 1965; Blinkova, Bresler & Lanzov, 1965; Gross & Caro, 1965).


2019 ◽  
Author(s):  
Sujan Devbhandari ◽  
Dirk Remus

ABSTRACTThe coordination of DNA unwinding and synthesis at replication forks promotes efficient and faithful replication of chromosomal DNA. Using the reconstituted budding yeast DNA replication system, we demonstrate that Pol ε variants harboring catalytic point mutations in the Pol2 polymerase domain, contrary to Pol2 polymerase domain deletions, inhibit DNA synthesis at replication forks by displacing Pol δ from PCNA/primer-template junctions, causing excessive DNA unwinding by the replicative DNA helicase, CMG, uncoupled from DNA synthesis. Mutations that suppress the inhibition of Pol δ by Pol ε restore viability in Pol2 polymerase point mutant cells. We also observe uninterrupted DNA unwinding at replication forks upon dNTP depletion or chemical inhibition of DNA polymerases, demonstrating that leading strand synthesis is not tightly coupled to DNA unwinding by CMG. Importantly, the Rad53 kinase controls excessive DNA unwinding at replication forks by limiting CMG helicase activity, suggesting a mechanism for fork-stabilization by the replication checkpoint.


1999 ◽  
Vol 19 (1) ◽  
pp. 835-845 ◽  
Author(s):  
Zeng-Feng Wang ◽  
Thomas C. Ingledue ◽  
Zbigniew Dominski ◽  
Ricardo Sanchez ◽  
William F. Marzluff

ABSTRACT Translationally inactive histone mRNA is stored in frog oocytes, and translation is activated at oocyte maturation. The replication-dependent histone mRNAs are not polyadenylated and end in a conserved stem-loop structure. There are two proteins (SLBPs) which bind the 3′ end of histone mRNA in frog oocytes. SLBP1 participates in pre-mRNA processing in the nucleus. SLBP2 is oocyte specific, is present in the cytoplasm, and does not support pre-mRNA processing in vivo or in vitro. The stored histone mRNA is bound to SLBP2. As oocytes mature, SLBP2 is degraded and a larger fraction of the histone mRNA is bound to SLBP1. The mechanism of activation of translation of histone mRNAs may involve exchange of SLBPs associated with the 3′ end of histone mRNA.


2005 ◽  
Vol 16 (3) ◽  
pp. 1527-1542 ◽  
Author(s):  
Soheil Naderi ◽  
Jean Y.J. Wang ◽  
Tung-Ti Chen ◽  
Kristine B. Gutzkow ◽  
Heidi K. Blomhoff

cAMP exerts an antiproliferative effect on a number of cell types including lymphocytes. This effect of cAMP is proposed to be mediated by its ability to inhibit G1/S transition. In this report, we provide evidence for a new mechanism whereby cAMP might inhibit cellular proliferation. We show that elevation of intracellular levels of cAMP inhibits DNA replication and arrests the cells in S phase. The cAMP-induced inhibition of DNA synthesis was associated with the increased binding of p21Cip1to Cdk2-cyclin complexes, inhibition of Cdk2 kinase activity, dephosphorylation of Rb, and dissociation of PCNA from chromatin in S phase cells. The ability of cAMP to inhibit DNA replication and trigger release of PCNA from chromatin required Rb and p21Cip1proteins, since both processes were only marginally affected by increased levels of cAMP in Rb-/-and p21Cip1-/-3T3 fibroblasts. Importantly, the implications of cAMP-induced inhibition of DNA synthesis in cancer treatment was demonstrated by the ability of cAMP to reduce apoptosis induced by S phase–specific cytotoxic drugs. Taken together, these results demonstrate a novel role for cAMP in regulation of DNA synthesis and support a model in which activation of cAMP-dependent signaling protects cells from the effect of S phase–specific antitumor agents.


1987 ◽  
Vol 7 (12) ◽  
pp. 4594-4598 ◽  
Author(s):  
C Gutierrez ◽  
Z S Guo ◽  
J Farrell-Towt ◽  
G Ju ◽  
M L DePamphilis

Antibodies against human c-myc protein have been reported to inhibit DNA polymerase activity and endogenous DNA synthesis in isolated nuclei, suggesting a role for c-myc in DNA replication. Using the same antibody preparations, we observed equivalent inhibition of simian virus 40 DNA replication and DNA polymerase alpha and delta activities in vitro, as well as inhibition of DNA synthesis in isolated nuclei. However, the c-myc antibodies could be completely separated from the DNA synthesis inhibition activity. c-myc antibodies prepared in other laboratories also did not interfere with initiation of simian virus 40 DNA replication, DNA synthesis at replication forks, or DNA polymerase alpha or delta activity. Therefore, the previously reported inhibition of DNA synthesis by some antibody preparations resulted from the presence of an unidentified inhibitor of DNA polymerases alpha and delta and not from the action of c-myc antibodies.


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