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261.
262.
S. G. Whittaker B. M. Rockmill A. E. Blechl D. H. Maloney M. A. Resnick S. Fogel 《Molecular & general genetics : MGG》1988,215(1):10-18
Summary A system is described in which spontaneous and chemically-induced mitotic and meiotic hyperploidy can be assayed in the same diploid culture of Saccharomyces cerevisiae. Monitoring gene dosage changes at two loci on chromosome VIII, the test utilizes a leaky temperature-sensitive allele arg4-8 and low level copper resistance conferred by the single copy allele cup1
s. An extra chromosome VIII provides simultaneous increased dosage for both genes, resulting in colonies that are both prototrophic for arginine at 30° C and copper resistant. During mitotic cell divisions in diploids, spontaneous chromosome VIII hyperploids (trisomes and tetrasomes) occur at a frequency of 6.4×10-6 per viable cell. Among ascospores, the spontaneous chromosome VIII disome frequency is 5.5×10-6 per viable spore. The tubulin-binding reagent methyl benzimidazol-2-yl carbamate (MBC) elicits enhanced levels of mitotic and meiotic aneuploidy relative to control levels. The system represents a novel model for examining chromosome behavior during mitosis and meiosis and provides a sensitive and quantifiable procedure for examining chemically induced aneuploidy. 相似文献
263.
Summary Extracts of Rad+ and radiation-sensitive (rad) mutants of the yeast Saccharomyces cerevisiae were examined for total Mg2+-dependent alkaline deoxyribonuclease activity and the presence of a nuclease that crossreacts immunologically with an antiserum raised against an endoexonuclease from Neurospora crassa, an enzyme exhibiting both deoxyribo- and ribonuclease activities. No significant differences were observed in total deoxyribonuclease activity between Rad+ and rad mutants. The antibody precipitable activity, however, was found to be 30%–40% of the total alkaline deoxyribonuclease activity in logarithmically growing Rad+ cells. Extracts of stationary phase cells were lacking in antibody precipitable activity. Using immunoblot methods, a 72 kDa crossreacting protein was identified from logarithmically growing cells that was absent from stationary phase cells. In all radiation-sensitive mutants examined, except rad52, at least 20% of total activity was precipitable. Extracts from logarithmically growing rad52 mutants, including a rad52::LEU2 insertion mutant, exhibited less than 10% of the Rad+ precipitable activity; however, some crossreacting material was detected. Although, the level of endo-exonuclease activity is influenced by the RAD52 gene, it is not the product of this gene. The total deoxyribonuclease and the antibody precipitable endo-exonuclease activities were also followed during meiosis. Unlike the Rad+ strain which had previously been shown to have increased levels of total and immunoprecipitable endo-exonuclease as cells underwent meiosis, the rad52 mutant exhibited no increases in either category of nuclease activity. Given the importance of the RAD52 gene in repair, recombination and mutagenesis, the endo-exonuclease may be a significant component of these processes. 相似文献
264.
Seven aprotic polar solvents which had previously been shown to interfere with the aggregation in vitro of porcine brain tubulin have been examined for their ability to induce mitotic aneuploidy in Saccharomyces cerevisiae in relation to temperature during exposure. Induction of aneuploidy was in general considerably enhanced when incubation at 28 degrees C was interrupted by overnight storage at low temperature (cold shock). The optimum cold-shock temperatures for individual chemicals varied over a range of 0-16 degrees C. While storage at reduced temperature enhanced the effect of treatment at 28 degrees C, it was also shown that continuous incubation at reduced temperature could greatly enhance the induction of aneuploidy. Only 2 chemicals, 1-methyl-2-pyrrolidinone and gamma-valerolactone, required cold shock to yield a positive response. The other chemicals did not require cold shock for enhanced induction. The observation that the agents examined also interfere with in vitro tubulin aggregation suggests that there is a temperature component to the interaction of these agents with tubulin in vivo. This temperature component is unusual in that the most effective temperature range for aneuploidy induction can be well below the optimal growth temperature for the test organism. 相似文献
265.
Michael A. Resnick James Westmoreland Enrique Amaya Kerry Bloom 《Molecular & general genetics : MGG》1987,210(1):16-22
Summary The centromere is the region within a chromosome that is required for proper segregation during mitosis and meiosis. Lesions in this sequence represent a unique type of damage, as loss of function could result in catastrophic loss of the genetic material of an entire chromosome. We have measured the induction by ultraviolet (UV) light of pyrimidine dimers in a 2550-bp restriction fragment that includes the centromere region of chromosome III in Saccharomyces cerevisiae. Yeast cells were exposed to ultraviolet light, cellular DNA was gently extracted, and subsequently treated with a UV-specific endonuclease to cleave all pyrimidine dimers. The sites of UV-specific nuclease scission within the centromere were determined by separating the DNA according to molecular weight, transferring the fragments to nitrocellulose, and hybridizing to a radiolabeled 624-bp fragment homologous to the centromere DNA from chromosome III. Several hotspots were identified in chromatin DNA from cells, as well as in irradiated deproteinized DNA. Double strand damage due to closely opposed pyrimidine dimers was also observed. At biological doses (35% survival) there are approximately 0.1 to 0.2 pyrimidine dimers per centromere. These dimers are efficiently repaired in the centromere and surrounding region. 相似文献
266.
Evolution of transposable elements: an IS10 insertion increases fitness in Escherichia coli 总被引:3,自引:0,他引:3
Strains of Escherichia coli carrying Tn10, a transposon consisting of two
IS10 insertion sequences flanking a segment encoding for a
tetracycline-resistance determinant, gain a competitive advantage in
chemostat cultures. All Tn10-bearing strains that increase in frequency
during competition have a new IS10 insertion that is found in the same
location in the genome of those strains. We mapped, by a gradient of
transmission, the position of the new IS10 insertion. We examined 11
isolates whose IS10 insertion was deleted by recombinational crossing-
over, and in all cases the competitive fitness of the isolates was
decreased. These results show that the IS10-generated insertion increases
fitness in chemostat cultures. We named the insertion fit::IS10 and suggest
that transposable elements may speed the rate of evolution by promoting
nonhomologous recombination between preexisting variations within a genome
and thereby generating adaptive variation.
相似文献
267.
Members of the ZFY and ZNF6 gene families have been cloned from species
representing different taxa and different modes of sex determination.
Comparisons of these genes show the ZFY-like and ZNF6 sequences to be
strongly conserved across marsupials, birds, and lepidosaurians. Sequence
analyzed by neighbor-joining indicated that both gene families are
monophyletic with a high bootstrap value. Pairing of sequences from males
and females of nonmammalian species showed there to be no significant
difference between male and female sequences from a single species,
consistent with autosomal locations. The molecular distances between murine
Zfy-1, Zfy-2, and other ZFY-like sequences suggested that Zfy genes have
undergone a period of rapid evolutionary change not seen in human ZFY.
相似文献
268.
Human Rhinovirus Type 14:Human Immunodeficiency Virus Type 1 (HIV-1) V3 Loop Chimeras from a Combinatorial Library Induce Potent Neutralizing Antibody Responses against HIV-1
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Allen D. Smith Sheila C. Geisler Anne A. Chen Dawn A. Resnick Birgit M. Roy Paul J. Lewi Edward Arnold Gail Ferstandig Arnold 《Journal of virology》1998,72(1):651-659
In an effort to develop a useful AIDS vaccine or vaccine component, we have generated a combinatorial library of chimeric viruses in which the sequence IGPGRAFYTTKN from the V3 loop of the MN strain of human immunodeficiency virus type 1 (HIV-1) is displayed in many conformations on the surface of human rhinovirus 14 (HRV14). The V3 loop sequence was inserted into a naturally immunogenic site of the cold-causing HRV14, bridged by linkers consisting of zero to three randomized amino acids on each side. The library of chimeric viruses obtained was subjected to a variety of immunoselection schemes to isolate viruses that provided the most useful presentations of the V3 loop sequence for potential use in a vaccine against HIV. The utility of the presentations was assessed by measures of antigenicity and immunogenicity. Most of the immunoselected chimeras examined were potently neutralized by each of the four different monoclonal anti-V3 loop antibodies tested. Seven of eight chimeric viruses were able to elicit neutralizing antibody responses in guinea pigs against the MN and ALA-1 strains of HIV-1. Three of the chimeras elicited HIV neutralization titers that exceeded those of all but a small number of previously described HIV immunogens. These results indicate that HRV14:HIV-1 chimeras may serve as useful immunogens for stimulating immunity against HIV-1. This method can be used to flexibly reconstruct varied immunogens on the surface of a safe and immunogenic vaccine vehicle. 相似文献
269.
Requirement for End-Joining and Checkpoint Functions, but Not RAD52-Mediated Recombination, after EcoRI Endonuclease Cleavage of Saccharomyces cerevisiae DNA 总被引:2,自引:0,他引:2
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L. Kevin Lewis Jakob M. Kirchner Michael A. Resnick 《Molecular and cellular biology》1998,18(4):1891-1902
RAD52 and RAD9 are required for the repair of double-strand breaks (DSBs) induced by physical and chemical DNA-damaging agents in Saccharomyces cerevisiae. Analysis of EcoRI endonuclease expression in vivo revealed that, in contrast to DSBs containing damaged or modified termini, chromosomal DSBs retaining complementary ends could be repaired in rad52 mutants and in G1-phase Rad+ cells. Continuous EcoRI-induced scission of chromosomal DNA blocked the growth of rad52 mutants, with most cells arrested in G2 phase. Surprisingly, rad52 mutants were not more sensitive to EcoRI-induced cell killing than wild-type strains. In contrast, endonuclease expression was lethal in cells deficient in Ku-mediated end joining. Checkpoint-defective rad9 mutants did not arrest cell cycling and lost viability rapidly when EcoRI was expressed. Synthesis of the endonuclease produced extensive breakage of nuclear DNA and stimulated interchromosomal recombination. These results and those of additional experiments indicate that cohesive ended DSBs in chromosomal DNA can be accurately repaired by RAD52-mediated recombination and by recombination-independent complementary end joining in yeast cells. 相似文献
270.