Effect of inhibition of DNA synthesis on histone synthesis and deposition

Biochemistry ◽  
1978 ◽  
Vol 17 (23) ◽  
pp. 4885-4893 ◽  
Author(s):  
Paul Nadeau ◽  
Denis R. Oliver ◽  
Roger Chalkley
1970 ◽  
Vol 55 (5) ◽  
pp. 688-702 ◽  
Author(s):  
Alan Johnson ◽  
Howard Rothstein

Histones have been electrophoretically separated from acid extracts of the frog lens for the first time. The five conventional histone fractions, representing four electrophoretic bands (f1; f2b, f3; f2a2; and f2a1), are present in both the epithelial and fiber cells. In addition, a fifth fraction was isolated from both sources and the evidence suggests that it may be a tissue-specific histone, possibly related to the lysine-rich f2c fraction found previously only in nucleated erythrocytes. The epithelial cells contain a substantially greater amount of histone than the fiber cells. Moreover, the fibers, unlike the epithelium, manifest no net histone synthesis or turnover following lenticular explantation. Microspectrophotometric, radioautographic, and gel electrophoretic studies indicate that the histones are synthesized in frog lenses concurrently with DNA. Inhibition of DNA synthesis does not completely abolish that of histones but reduces it by about one-half. In the early stages of culture (prior to their synthesis and that of DNA) the histones appear to undergo alterations which are prevented by treatment with cycloheximide.


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.


2002 ◽  
Vol 22 (21) ◽  
pp. 7459-7472 ◽  
Author(s):  
David M. Nelson ◽  
Xiaofen Ye ◽  
Caitlin Hall ◽  
Hidelita Santos ◽  
Tianlin Ma ◽  
...  

ABSTRACT DNA and histone synthesis are both triggered at the beginning of S phase by cyclin/cdk2 activity. Previous studies showed that inhibition of DNA synthesis with hydroxyurea or cytosine arabinoside (AraC) triggers a concerted repression of histone synthesis, indicating that sustained histone synthesis depends on continued DNA synthesis. Here we show that ectopic expression of HIRA, the likely human ortholog of two cell cycle-regulated repressors of histone gene transcription in yeast (Hir1p and Hir2p), represses transcription of histones and that this, in turn, triggers a concerted block of DNA synthesis. Thus, in mammalian cells sustained DNA synthesis and histone synthesis are mutually dependent on each other during S phase. Although cyclin/cdk2 activity drives activation of both DNA and histone synthesis at the G1/S transition of cycling cells, concerted repression of DNA or histone synthesis in response to inhibition of either one of these is not accompanied by prolonged inhibition of cyclin A/cdk2 or E/cdk2 activity. Therefore, during S phase coupling of DNA and histone synthesis occurs, at least in part, through a mechanism that is independent of cyclin/cdk2 activity. Coupling of DNA and histone synthesis in S phase presumably contributes to the prompt and orderly assembly of newly replicated DNA into chromatin.


1992 ◽  
Vol 267 (2) ◽  
pp. 691-694 ◽  
Author(s):  
V J LaMorte ◽  
P K Goldsmith ◽  
A M Spiegel ◽  
J L Meinkoth ◽  
J R Feramisco

1990 ◽  
Vol 25 (6) ◽  
pp. 418-424 ◽  
Author(s):  
Li-Ming Wang ◽  
J. Courtland White ◽  
Robert L. Capizzi

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