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1.
Genome rearrangement in top3 mutants of Saccharomyces cerevisiae requires a functional RAD1 excision repair gene. 下载免费PDF全文
Saccharomyces cerevisiae cells that are mutated at TOP3, a gene that encodes a protein homologous to bacterial type I topoisomerases, have a variety of defects, including reduced growth rate, altered gene expression, blocked sporulation, and elevated rates of mitotic recombination at several loci. The rate of ectopic recombination between two unlinked, homologous loci, SAM1 and SAM2, is sixfold higher in cells containing a top3 null mutation than in wild-type cells. Mutations in either of the two other known topoisomerase genes in S. cerevisiae, TOP1 and TOP2, do not affect the rate of recombination between the SAM genes. The top3 mutation also changes the distribution of recombination events between the SAM genes, leading to the appearance of novel deletion-insertion events in which conversion tracts extend beyond the coding sequence, replacing the DNA flanking the 3' end of one SAM gene with nonhomologous DNA flanking the 3' end of the other. The effects of the top3 null mutation on recombination are dependent on the presence of an intact RAD1 excision repair gene, because both the rate of SAM ectopic gene conversion and the conversion tract length were reduced in rad1 top3 mutant cells compared with top3 mutants. These results suggest that a RAD1-dependent function is involved in the processing of damaged DNA that results from the loss of Top3 activity, targeting such DNA for repair by recombination. 相似文献
2.
Julie M. Bailis Marcia L. Gordon Jesse L. Gurgel Alexis C. Komor Jacqueline K. Barton Ilan R. Kirsch 《PloS one》2013,8(10)
The DNA mismatch repair system (MMR) maintains genome stability through recognition and repair of single-base mismatches and small insertion-deletion loops. Inactivation of the MMR pathway causes microsatellite instability and the accumulation of genomic mutations that can cause or contribute to cancer. In fact, 10-20% of certain solid and hematologic cancers are MMR-deficient. MMR-deficient cancers do not respond to some standard of care chemotherapeutics because of presumed increased tolerance of DNA damage, highlighting the need for novel therapeutic drugs. Toward this goal, we generated isogenic cancer cell lines for direct comparison of MMR-proficient and MMR-deficient cells. We engineered NCI-H23 lung adenocarcinoma cells to contain a doxycycline-inducible shRNA designed to suppress the expression of the mismatch repair gene MLH1, and compared single cell subclones that were uninduced (MLH1-proficient) versus induced for the MLH1 shRNA (MLH1-deficient). Here we present the characterization of these MMR-inducible cell lines and validate a novel class of rhodium metalloinsertor compounds that differentially inhibit the proliferation of MMR-deficient cancer cells. 相似文献
3.
4.
This study estimates global warming impact (GWI) of E85 fuel needed to run a small passenger car for its average lifetime, i.e., 241,402 km (150,000 miles). The ethanol needed for the production of E85 fuel was derived from an intensively managed slash pine (Pinus elliottii) plantation in the southern USA. We assumed that only pulpwood and harvesting residues obtained at the time of harvesting were used for ethanol production. A suitable system boundary was defined and a detailed life-cycle assessment was undertaken to determine GWI of all the steps present within the system boundary. Results indicate that the overall GWI of the E85 fuel was about 76% less than an equivalent amount of gasoline needed to run a small passenger car for its average lifetime. Within the system boundary, the GWI of the ethanol production stage was highest followed by the stage of E85 fuel consumption in a small passenger car. A need exists to evaluate impacts of utilizing forest biomass for E85 fuel production on forest ecology and traditional forest biomass-based industries. 相似文献
5.
The effect of food deprivation on ova transport, hormonal profiles and metabolic changes was studied in 20 crossbred multiparous
sows during their second oestrus after weaning. To determine the time of ovulation, transrectal ultrasonographic examination
was performed. The sows were divided into 2 groups, one control group (C-group), which was fed according to Swedish standards,
and one experimental group (E-group). The E-group sows were deprived of food from the first morning meal after ovulation until
slaughter. Blood samples were collected every second hour from about 12 h before expected ovulation in the second oestrus
after weaning until slaughter and were analysed for progesterone, prostaglandin F2α-metabolite, insulin, glucose, free fatty acids and triglycerides. All sows were slaughtered approximately 48 h after ovulation
and the genital tract was recovered. The isthmic part of the oviduct was divided into 3 equally long segments and flushed
separately with phosphate buffered saline (PBS). Uterine horns were also flushed with PBS. A significantly greater number
of ova were found in the first and second part of the isthmus in the E-group (p = 0.05) while in the C-group most of the ova
were found in the third part of the isthmus or the uterus (p = 0.01). The level of prostaglandin F2α-metabolite was significantly higher in the E-group compared with the C-group. The concentration of progesterone increased
in both groups after ovulation but there were no significant differences between the groups. The other blood parameters showed
that the food-deprived sows were in a catabolic state. The 48 h period of fasting results, directly or indirectly in an delayed
ova transport, which may be due to a delayed relaxation in the smooth circular muscle layer of the isthmus. 相似文献
6.
7.
Regulation of phospholipid biosynthesis in Saccharomyces cerevisiae by inositol. Inositol is an inhibitor of phosphatidylserine synthase activity 总被引:12,自引:0,他引:12
M J Kelley A M Bailis S A Henry G M Carman 《The Journal of biological chemistry》1988,263(34):18078-18085
The addition of inositol to the growth medium of Saccharomyces cerevisiae resulted in rapid changes in the rates of phospholipid biosynthesis. The partitioning of the phospholipid intermediate CDP-diacylglycerol was shifted to phosphatidylinositol at the expense of phosphatidylserine and its derivatives phosphatidylethanolamine and phosphatidylcholine. Serine at 133-fold greater concentrations than that of inositol shifted the partitioning of CDP-diacylglycerol to phosphatidylserine at the expense of phosphatidylinositol but to a much lesser degree. Kinetic experiments with pure phosphatidylserine synthase and phosphatidylinositol synthase indicated that the partitioning of CDP-diacylglycerol between phosphatidylserine and phosphatidylinositol was not governed by the affinities both enzymes have for their common substrate CDP-diacylglycerol. Instead, the main regulation of phosphatidylinositol and phosphatidylserine synthesis was through the exogenous supply of inositol. The Km of inositol (0.21 mM) for phosphatidylinositol synthase was 9-fold higher than cytosolic concentration of inositol (24 microM). The Km of serine (0.83 mM) for phosphatidylserine synthase was 3-fold below the cytosolic concentration of serine (2.6 mM). Therefore, inositol supplementation resulted in a dramatic increase in the rate of phosphatidylinositol synthesis, whereas serine supplementation resulted in little affect on the rate of phosphatidylserine synthesis. Inositol also contributed to the regulation of phosphatidylinositol and phosphatidylserine synthesis by having a direct affect on phosphatidylserine synthase activity. Kinetic experiments with pure phosphatidylserine synthase showed that inositol was a noncompetitive inhibitor of the enzyme with a Ki of 65 microM. 相似文献
8.
Coordinate regulation of phospholipid biosynthesis by serine in Saccharomyces cerevisiae. 总被引:2,自引:4,他引:2 下载免费PDF全文
The addition of L-serine to inositol-containing growth medium repressed membrane-associated CDPdiacylglycerol synthase (CTP:phosphatidate cytidylyltransferase, EC 2.7.7.41) and phosphatidylserine synthase (CDPdiacylglycerol:L-serine O-phosphatidyltransferase, EC 2.7.8.8) activities and subunit levels in wild-type Saccharomyces cerevisiae. Enzyme activities and subunit levels were not repressed when inositol was absent from the growth medium. The addition of L-serine to the growth medium did not affect the phospholipid composition of wild-type cells. CDPdiacylglycerol synthase and phosphatidylserine synthase were not regulated in the S. cerevisiae inositol biosynthesis ino2, ino4, and opi1 regulatory mutants, suggesting that regulation by inositol plus L-serine is coupled to inositol synthesis. Inositol and L-serine did not affect the activities of purified CDPdiacylglycerol synthase and phosphatidylserine synthase. The addition of compounds structurally related to L-serine to the growth medium of wild-type cells also resulted in a repression of CDPdiacylglycerol synthase and phosphatidylserine synthase but only in the presence of inositol. Phosphatidylinositol synthase (CDPdiacylglycerol:myo-inositol 3-phosphatidyltransferase, EC 2.7.8.11) was not regulated by inositol plus L-serine. 相似文献
9.
The membrane-associated enzyme phosphatidylserine synthase is regulated at the level of mRNA abundance. 总被引:25,自引:2,他引:25 下载免费PDF全文
To precisely define the functional sequence of the CHO1 gene from Saccharomyces cerevisiae, encoding the regulated membrane-associated enzyme phosphatidylserine synthase (PSS), we subcloned the original 4.5-kilobase (kb) CHO1 clone. In this report a 2.8-kb subclone was shown to complement the ethanolamine-choline auxotrophy and to repair the defect in the synthesis of phosphatidylserine, both of which are characteristic of cho1 mutants. When this subclone was used as a hybridization probe of Northern and slot blots of RNA from wild-type cells, the abundance of a 1.2-kb RNA changed in response to alterations in the levels of the soluble phospholipid precursors inositol and choline. The addition of inositol led to a 40% repression of the 1.2-kb RNA level, while the addition of choline and inositol led to an 85% repression. Choline alone had little repressive effect. The level of 1.2-kb RNA closely paralleled the level of PSS activity found in the same cells as determined by enzyme assays. Disruption of the CHO1 gene resulted in the simultaneous disappearance of 1.2-kb RNA and PSS activity. Cells bearing the ino2 or ino4 regulatory mutations, which exhibit constitutively repressed levels of a number of phospholipid biosynthetic enzymes, had constitutively repressed levels of 1.2-kb RNA and PSS activity. Another regulatory mutation, opi1, which causes the constitutive derepression of PSS and other phospholipid biosynthetic enzymes, caused the constitutive derepression of the 1.2-kb RNA. When cho1 mutant cells were transformed with the 2.8-kb subclone on a single-copy plasmid, the 1.2-kb RNA and PSS activity levels were regulated in a wild-type fashion. The presence of the 2.8-kb subclone on a multicopy plasmid, however, led to the constitutive overproduction of 1.2-kb RNA and PSS in cho1 cells. 相似文献
10.
Juan Manuel Herrero-Medrano Hendrik-Jan Megens Martien AM Groenen Mirte Bosse Miguel Pérez-Enciso Richard PMA Crooijmans 《BMC genomics》2014,15(1)