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THE REGULATION OF HISTONE AND HISTONE MESSENGER-RNA SYNTHESIS DURING THE CELL CYCLE

Histones are synthesized coordinately with DNA during the S phase of the cell cycle. However, mouse myeloma cells synchronized by isoleucine starvation synthesize increased amounts of H1 relative to the core histones. The synthesis of H1 increases coordinately again with core histones during S phase. Hydroxyurea blocks the H1 synthesis in isoleucine-starved cells but cytosine arabinoside only partially inhibits this H1 synthesis. When cells were starved for lysine, the relative proportion of the H1 synthesized was much lower than normal. These changes in relative ratios of synthesis are reflected in changes in mRNA levels. Although these phenomena can be explained by a "trivial" translational mechanism, 3T3 cells starved for serum also synthesized proportionally higher amounts of H1 as compared to core histones. The increased H1 synthesis in isoleucine starved cells could be the very reason why isoleucine starvation arrests cultured mammalian cells in G(,1). / Our recent isolation of mouse histone genes (Sittman et al., Proc. Natl. Acad. Sci. 78, 4078 (1981) allows quantitation of the levels of histone mRNA in cultured mammalian cells. I have measured the levels of H3 and H2b mRNA by Northern hybridization and in vitro translation in four cell lines: myeloma cells synchronized by isoleucine starvation, 3T3 cells synchronized by serum starvation, lymphoma S49 cells selected at G(,1) or S phase by centrifugal elutriation, and CHO cells synchronized by mitotic shake-off. The results indicate that histone mRNA levels are regulated during the cell cycle. However, there are significant levels of histone mRNA found in G(,1) in myeloma cells, S49 cells and CHO cells (30-50% of S phase). These RNAs accumulate in G(,1) in myeloma cells during isoleucine starvation. In contrast, 3T3 cells arrested in G(,1) by serum starvation do not contain detectable (< 2%) histone mRNA. One step of the regulation is at the level of RNA turnover. Treatment with hydroxyurea reduced histone mRNA levels by 85% in one hour. These results are consistent with histone mRNA synthesis being initiated in G(,1) and the mRNA being destroyed at the end of S phase. / Source: Dissertation Abstracts International, Volume: 42-10, Section: B, page: 4043. / Thesis (Ph.D.)--The Florida State University, 1981.

Identiferoai:union.ndltd.org:fsu.edu/oai:fsu.digital.flvc.org:fsu_74674
ContributorsCHIU, ING-MING., Florida State University
Source SetsFlorida State University
Detected LanguageEnglish
TypeText
Format176 p.
RightsOn campus use only.
RelationDissertation Abstracts International

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