Rates of synthesis of ribosomal protein and total ribonucleic acid through the cell cycle of the fission yeast Schizosaccharomyces pombe

Wain, W.H.; Staatz, William D.

doi:10.1016/0014-4827(73)90515-6

Cited by 38 publications

(20 citation statements)

References 23 publications

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“…During the mid-to-late 1970s, several studies aimed to determine whether ribosome biogenesis in yeast is cell cycle regulated in the same manner as in metazoan cells (Shulman et al, 1973;Wain and Staatz, 1973;Sogin et al, 1974;Elliot and McLaughlin, 1979). Collectively, these studies revealed that the rate of synthesis of the mature rRNAs remained constant throughout the cell cycle, suggesting that ribosome biogenesis is not cell cycle regulated in yeast.…”

Section: Introductionmentioning

confidence: 99%

“…Links between ribosome biogenesis and the p53 pathway also have been observed by others (David-Pfeuty et al, 2001). Many of the proteins required for ribosome biogenesis have conserved orthologues, suggesting that these processes occur through similar mechanisms in all eukaryotes.During the mid-to-late 1970s, several studies aimed to determine whether ribosome biogenesis in yeast is cell cycle regulated in the same manner as in metazoan cells (Shulman et al, 1973;Wain and Staatz, 1973;Sogin et al, 1974;Elliot and McLaughlin, 1979). Collectively, these studies revealed that the rate of synthesis of the mature rRNAs remained constant throughout the cell cycle, suggesting that ribosome biogenesis is not cell cycle regulated in yeast.…”

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The Small Subunit Processome Is Required for Cell Cycle Progression at G1

Bernstein

Baserga

2004

MBoC

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Without ribosome biogenesis, translation of mRNA into protein ceases and cellular growth stops. We asked whether ribosome biogenesis is cell cycle regulated in the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe, and we determined that it is not regulated in the same manner as in metazoan cells. We therefore turned our attention to cellular sensors that relay cell size information via ribosome biogenesis. Our results indicate that the small subunit (SSU) processome, a complex consisting of 40 proteins and the U3 small nucleolar RNA necessary for ribosome biogenesis, is not mitotically regulated. Furthermore, Nan1/Utp17, an SSU processome protein, does not provide a link between ribosome biogenesis and cell growth. However, when individual SSU processome proteins are depleted, cells arrest in the G1 phase of the cell cycle. This arrest was further supported by the lack of staining for proteins expressed in post-G1. Similarly, synchronized cells depleted of SSU processome proteins did not enter G2. This suggests that when ribosomes are no longer made, the cells stall in the G1. Therefore, yeast cells must grow to a critical size, which is dependent upon having a sufficient number of ribosomes during the G1 phase of the cell cycle, before cell division can occur. INTRODUCTIONRibosomes are essential for the translation of mRNA into protein and are necessary for cell growth. Synthesis of the small and large ribosomal subunits begins with the transcription of rDNA into a single 35S pre-rRNA transcript within the cell nucleolus. In yeast, the 35S pre-rRNA is processed into the 5.8S, 18S, and 25S rRNAs. Pre-rRNA processing occurs through distinct pathways at 10 known processing sites by many trans-acting factors, including small nucleolar ribonucleoproteins (snoRNPs; Lafontaine and Tollervey, 1995;Kressler et al., 1999;Gerbi et al., 2001Gerbi et al., , 2003. The 18S rRNA is incorporated into the small ribosomal subunit, whereas the 5.8S and 25S rRNAs are incorporated into the large ribosomal subunit. The two ribosomal subunits are transported from the nucleolus through the nucleoplasm to the cytoplasm where they are assembled into a fully functional ribosome.The cellular sensors that coordinate ribosome biogenesis and cell division are largely unknown (Jorgensen et al., 2002). Cell cycle regulation of ribosome biogenesis was first observed in metazoan cells, where several laboratories reported a lack of RNA synthesis in mitotic cells (Taylor, 1960;Prescott and Bender, 1962). Since then, others have shown that both pre-rRNA transcription and processing cease during mitosis in mammalian cells (Gautier et al., 1994;Dundr and Olson, 1998;Sirri et al., 2000). When mitotic transcription of the pre-rRNA is forced by inhibition of cdc2-cyclin B kinase, defects in processing of the pre-rRNA are observed (Sirri et al., 2000). These results indicate that both transcription and processing of the pre-rRNA are inhibited during mitosis in mammalian cells.Recently, ribosome biogenesis has been linked to the cell cycle thr...

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Section: Introductionmentioning

confidence: 99%

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The Small Subunit Processome Is Required for Cell Cycle Progression at G1

Bernstein

Baserga

2004

MBoC

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“…In Aspergillus fumigatus, the catabolite and a-fluoro-,-alanine were also detected (3). Although 5-FC and its derivatives can be readily detected in the soluble pool of intact cells, it is not possible to detect these compounds once they are incorporated into cellular macromolecules without prior degradation (20,26).From biochemical studies, it is known that in yeasts 5-FC is deaminated to 5-FU and that 5-FU is subsequently phosphorylated to 5-FUMP and 5-FUDP. This latter compound can be converted to either 5-FUTP or to 5-fluoro-2'-deoxyuridine-5'-monophosphate (5-FdUMP), which, together or independently, determine the antifungal activity of 5-FC via production of aberrant RNA or inhibition of DNA synthesis, respectively (21, 25) (Fig.…”

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19F nuclear magnetic resonance study of fluoropyrimidine metabolism in strains of Candida glabrata with specific defects in pyrimidine metabolism

Fasoli

Kerridge

Morris

et al. 1990

Antimicrob Agents Chemother

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Flucytosine (5-FC)-resistant strains were isolated from the haploid opportunistic pathogen Candida glabrata by UV-induced mutation and fluoropyrimidine selection. These strains were characterized biochemically, and the metabolism of fluorinated pyrimidines was studied by '9F nuclear magnetic resonance spectroscopy. No evidence was obtained from these studies for degradative metabolism of the fluorinated derivatives. In the parental susceptible strain of C. glabrata, 5-fluorouracil but not 5-FC was detected within the cells. 5-Fluorouracil was also present in the culture supernatant after incubation of the cells with 5-FC. The distribution of fluorinated derivatives within the 5-FC-resistant strains was consistent with their genotype. Two strains of C. glabrata which had only a partial loss of cytosine deaminase and UMP pyrophosphorylase activity had high levels of resistance to 5-FC. Both C. glabrata and Candida albicans were susceptible to 5-fluorouridine. This compound but not the anticancer drug 5-fluoro-2-deoxyuridine was shown to be transported into susceptible cells by a specific uridine permease.Nuclear magnetic resonance (NMR) spectroscopy is a powerful method for identifying drug metabolites (33) and investigating drug-receptor interactions in cell-free solutions (13). It can also be used noninvasively to study metabolism in vivo in microorganisms, isolated tissues, intact animals, or humans (18). The practical application of NMR spectroscopy in these living systems, however, is limited by sensitivity considerations.The "9F nucleus has the second-highest NMR sensitivity of the stable nuclei (ca. 85% of that of 'H at constant field). It is the naturally occurring isotope of fluorine (100% natural abundance) and is not present in living systems to any significant degree. The (6) and, more recently, in the liver (22, 31), plasma, and urine (8) of patients undergoing chemotherapy. In addition, it has been used to demonstrate tumor trapping of 5-FU in tumorbearing humans and rabbits (32). NMR spectroscopy has also been successful in demonstrating the existence of two distinct pathways of 5-FU degradation in E. coli (14).'9F NMR spectroscopy has also been employed in a preliminary study of the uptake and metabolism of the clinical antifungal drug 5-flucytosine (5-FC) in the medically important yeast Candida albicans (10). A similar but more quantitative approach was adopted to study 5-FC metabolism in three C. albicans strains and one Candida tropicalis * Corresponding author. strain (25). Results from these studies complemented each other and were consistent with the assigned genotypes of the strains used; in addition, they established the basic conditions under which "9F NMR spectroscopy may be used to obtain significant information on 5-FC metabolism in viable cells of Candida spp. Similar studies have been reported with Aspergillus spp. in which it has been shown that the main pathway of 5-FC metabolism is via the pyrimidine salvage pathway to 5-fluorouridine triphosphate (5-FUTP). In Aspergillus fumig...

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“…With respect to net uptake rate of all (major) nutrients that enter the cell, a linear growth model would predict constancy in uptake rates per cell with a doubling in rate at a certain stage in the cell cycle, whereas the exponential model would predict continuously increasing uptake rates (Kubitschek & Claymen, 1976;Kubitschek & Edvenson, 1977). Constancy of uptake rates (per cell) of adenine and serine during the G1 and G2/M phases of the cell cycle of S. cerevisiae and doubling of the uptake rates during the S phase were considered to be in agreement with linear growth (Kubitschek & Edvenson, 1977 Mitchison (1957) and by Wain & Staatz (1973). Thus, the apparent differences between.S.…”

Section: Discussionmentioning

confidence: 99%