Histones synthesis

Goldberg, R. B., Geremia, R., and Bruce, W. R. (1977). Histone synthesis and replacement during spermatogenesis in the mouse. Differentiation 7 167-180. 

The association of histones to one or the other of the strands can be distinguished using electron microscopy of material from cells grown under conditions where protein (i.e. histone) synthesis is inhibited but DNA synthesis is not inhibited. 

Histone Synthesis Histone Transfer into the Nudeus... 

Wu, R.S. and Bonner, W.M. (1981) Separation of basal histone synthesis from S-phase histone synthesis in dividing cells. Cell 27, 321-330. 

Waterborg, J.H. (1993) Histone synthesis and turnover in alfalfa. Fast loss of highly acetylated replacement histone variant H3.2. J. Biol. Chem. 268, 4912-4917. 

The temporal sequence of H3 and H4 methylation after synthesis has been examined in Ehrlich ascites tumor cells [144] and trout testis [149]. Methylation lagged histone synthesis, and the histone was methylated after being bound to DNA. H4 methylation follows the stepwise acetylations and deacetylations [149]. It was suggested that methylation was involved in final arrangement of H3 and H4 on newly replicated DNA [144] and might be involved in histone interactions with other proteins such as histone kinases [149]. 

Eukaryotic DNA is replicated at a slower rate than prokaryotic DNA. One reason may be the requirement for the deposition of histone proteins on DNA (histone synthesis and DNA replication are coupled). Describe a model for the replication of eukaryotic DNA and nucleosome formation. 

DNA in eukaryotic chromosomes is complexed with histone proteins in complexes called nucleosomes. These DNA-protein complexes are disassembled directly in front of the replication fork. The nucleosome disassembly may be rate-limiting for the migration of the replication forks, as the rate of migration is slower in eukaryotes than prokaryotes. The length of Okazaki fragments is also similar to the size of the DNA between nucleosomes (about 200 bp). One model that would allow the synthesis of new eukaryotic DNA and nucleosome formation would be the disassembly of the histones in front of the replication fork and then the reassembly of the histones on the two duplex strands. Histone synthesis is closely coupled to DNA replication. 

Thus, in some cells, parental histones appear to be inherited directly. Simian virus 40 may be an exception. When DNA synthesis ceases at the end of the S phase, any histone mRNA is rapidly degraded. This link between DNA synthesis and histone synthesis may serve as a feedback mechanism to ensure that the amount of new histone formed is consonant with the amount of new DNA synthesized. 

Wiekowski, M., Miranda, M., Nothias, J.-Y., and DePamphilis, M.L, (1997). Changes in histone synthesis and modification at the beginning of mouse development correlate with the establishment of chromatin mediated repression of transcription. J. Cell Sci. 110 1147-1158. Wilmut, 1., Schnieke, A.E., McWhir, J Kind, A.J., and Campbell, K.H. (1997). Viable offspring derived from fetal and adult mammalian cells. Nature 585 810-813. 

Reflect and Apply Would it be advantageous to a eukaryotic cell to have histone synthesis take place at a faster rate than DNA synthesis ... 

If histone synthesis took place faster than DNA synthesis, it would be highly disadvantageous to invest the energy required for protein synthesis. The histones would have no DNA with which to bind. 

In HeLa ceils hydroxyurea is an efficient inhibitor of histone synthesis. This action requires protein synthesis and leads to rapid disappearance of cytoplasmatic histone mRNA The effect is not specific for hydroxyurea since suppression of DNA synthesis by arabino-cytosine or temperature-sensitive mutations yields analogous results. Similarly, the synthesis of some enzymes necessary for DNA replication and active in S-phase is altered by hydroxyurea. Increased activity of ribonucleotide reductase in HeLa and in hamster cells and of the salvage enzyme thymidine kinase in HeLa cells and KB cells has been observed, probably as a consequence of the increased fraction of cells in S-phase. Repression occurs for thymidine kinase in human lymphocytes and for ornithine decarboxylase in Chinese hamster fibroblasts whereas no or only slight effects were seen on ribonucleotide reductase in hamster fibroblasts , on thymidylate synthase in extracts from synchronous mouse cells " , and on DNA polymerase in rabbit kidney cells or HeLa cells . ... 

In many eukaryotes, there are multiple copies of histone genes and this may allow a rapid rate of histone synthesis particularly during embryonic development. In the axolotl, there are as many as 1600 copies, whereas in yeast there are only two. Avian species do have multiple copies, although the number is modest (see below) compared with many other eukaryotes. The rapid rate of histone synthesis required during embryonic chick development appears to be achieved by having a high steady-state level of... 

Kawaichi M, Ueda K, Hayaishi O (1980) Initiation of poly(ADP-ribosyl) histone synthesis by poly(ADP-ribose) synthetase. J Biol Chem 255 816-819... 

Because of the apparent correlation between alkylation and derepression of DNA, Pogo, Allfrey, and Mirsky [71, 72] studied the incorporation of [ C]ace-tateinto histone [ " C]uridine into RNA [ C]thymi-dine into DNA and [ " C]alanine into protein of phy-tohemagglutinin-stimulated lymphocytes. Acetylation preceded RNA synthesis, which itself preceded the synthesis of some of the protein. DNA and histone synthesis occurred late in the sequence of events that followed phytohemagglutinin stimulation. The fact that histone acetylation preceded nuclear RNA synthesis was considered evidence that acetylation signals derepression of DNA. 

Histone acetylation has been observed in the salivary chromosomes of Chironomus thummi when RNA synthesis is active. Although acetylation can be demonstrated by radioautographic methods, there seems to be no way to measure its extent exactly. It is not known whether histone acetylation and RNA synthesis are related and, for example, if histone synthesis is a necessary prerequisite for the synthesis of RNA [73]. 

Phosphorylation of histones is another mechanism for the neutralization of basic proteins. The phosphorylation reaction occurs after the completion of the histone synthesis. It is reversible. Phosphorylation of the lysine- and arginine-rich histones precedes an increase in RNA synthesis. This was found in transforming lymphocytes, in the regenerating liver and pancreas, etc. Histones and protamines are phosphorylated at the final stages of spermatogenesis (see review of Allfrey et al, 1964, 1972). Specific kinases which participated in the transport of phosphorus groups from ATP to histones are stimulated by cyclic AMP (Allfrey et al., 1972). 

Rapopport, 1965) frees us from Ihe need to examine the general biochemical aspects of histone synthesis. We shall merely consider those of its other aspects which are to some degree connected with the discussion of their genetic functions. 

Monesi, V. Autoradiographic evidence of a nuclear histone synthesis during mouse spermiogenesis in the absence of detectable quantities of nuclear ribonucleic acid. Exp. Cell Res. 36, 683—688 (1964). 

Actinomycin D, added early in the S phase, prevents DNA replication in the late S phase (Mueller and Kajiwara, 1966). If added two or more hours after the initiation of DNA replication, actinomycin D does hot inhibit DNA replication. These observations are consistent with the view that actinomycin D inhibits synthesis of the RNA needed for the priming of DNA synthesis (Komberg, 1976). The addition of cyclohex-imide and puromycin to a growing cell causes a prompt decrease in the rate of DNA synthesis (Hand and Tamm, 1973 Seki and Mueller, 1975). This may represent inhibition of histone synthesis in the cytoplasm. 

Histone synthesis is initiated with the universal initiator methio-nyl-tRNA (Jacobs-Lorena and Baglioni, 1973). As the histone polypeptide is synthesized, the methionyl group is removed and the N-terminal serine is acetylated (Pestana and Pitot, 1974). The newly synthesized histone is transported within 10 s into the nucleus (Weintraub, 1972). 

Jacobs-Lorena, M., and Baglioni, C., 1973, Initiation of histone synthesis by f-met-tRNAf in an ascites cell-free system. Mol. Biol. Rep. 1 113. 

Pederson, T., and Robbins, E., 1970, Absence of translational control of histone synthesis during the HeLa cell life cycle, J. Cell Biol. 45 509. 

The cistron for globin would be selected, stabilized, and transferred to the cytoplasm, whereas the remaining RNA of this product would be degraded. At present there is little evidence on the basis of which one may choose between these possibilities. It is relevant to note, however, that treatment of avian erythrocytes with actinomycin D may result in inhibition of histone synthesis while the synthesis of hemoglobin is unimpaired (Freedman et al, 1966), a finding which would favor the first interpretation. 

Freedman, M. L., Honig, G. R., and Rabinovitz, M. (1966). The role of newly synthesized RNA on nuclear histone synthesis by chicken immature erythrocytes. Exptl. Cell Res. 44, 263-272. 

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