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Biomedical subjects

S Prakash

Publications and source records attributed to S Prakash.

At least 235 records · Page 13Linked to original sources
PubMed1990

The SRS2 suppressor of rad6 mutations of Saccharomyces cerevisiae acts by channeling DNA lesions into the RAD52 DNA repair pathway.

rad6 mutants of Saccharomyces cerevisiae are defective in the repair of damaged DNA, DNA damage induced mutagenesis, and sporulation. In order to identify genes that can substitute for RAD6 function, we have isolated genomic suppressors of the UV sensitivity of rad6 deletion (rad6 delta) mutations and show that they also suppress the gamma-ray sensitivity but not the UV mutagenesis or sporulation defects of rad6. The suppressors show semidominance for suppression of UV sensitivity and dominance for suppression of gamma-ray sensitivity. The six suppressor mutations we isolated are all alleles of the same locus and are also allelic to a previously described suppressor of the rad6-1 nonsense mutation, SRS2. We show that suppression of rad6 delta is dependent on the RAD52 recombinational repair pathway since suppression is not observed in the rad6 delta SRS2 strain containing an additional mutation in either the RAD51, RAD52, RAD54, RAD55 or RAD57 genes. Possible mechanisms by which SRS2 may channel unrepaired DNA lesions into the RAD52 DNA repair pathway are discussed.

Alleles↗
PubMed1990

N,N-diethylphenylacetamide--a new repellent for Periplaneta americana (Dictyoptera: Blattidae), Blattella germanica, and Supella longipalpa (Dictyoptera: Blattellidae).

The residual repellency of N,N-diethylphenylacetamide (DEPA) was studied against American cockroach, Periplaneta americana (L.); German cockroach, Blattella germanica (L.); and brownbanded cockroach, Supella longipalpa (F.) at various concentrations. DEPA exhibited residual repellency for 4, 3, and 2 wk against American, German, and brownbanded cockroach, respectively, at a concentration of 0.5 mg/cm2.

Acetamides↗
PubMed1990

RAD10, an excision repair gene of Saccharomyces cerevisiae, is involved in the RAD1 pathway of mitotic recombination.

The RAD10 gene of Saccharomyces cerevisiae is required for the incision step of excision repair of UV-damaged DNA. We show that the RAD10 gene is also required for mitotic recombination. The rad10 delta mutation lowered the rate of intrachromosomal recombination of a his3 duplication in which one his3 allele has a deletion at the 3' end and the other his3 allele has a deletion at the 5' end (his3 delta 3' his3 delta 5'). The rate of formation of HIS3+ recombinants in the rad10 delta mutant was not affected by the rad1 delta mutation but decreased synergistically in the presence of the rad10 delta mutation in combination with the rad52 delta mutation. These observations indicate that the RAD1 and RAD10 genes function together in a mitotic recombination pathway that is distinct from the RAD52 recombination pathway. The rad10 delta mutation also lowered the efficiency of integration of linear DNA molecules and circular plasmids into homologous genomic sequences. We suggest that the RAD1 and RAD10 gene products act in recombination after the formation of the recombinogenic substrate. The rad1 delta and rad10 delta mutations did not affect meiotic intrachromosomal recombination of the his3 delta 3' his3 delta 5' duplication or mitotic and meiotic recombination of ade2 heteroalleles located on homologous chromosomes.

Chromosome Deletion↗
PubMed1990

The Saccharomyces cerevisiae DNA repair gene RAD2 is regulated in meiosis but not during the mitotic cell cycle.

The expression of the RAD2 gene of Saccharomyces cerevisiae is elevated upon DNA damage. Here, we show that RAD2 transcript levels also rise approximately eightfold during meiosis but remain constant during the mitotic cell cycle. The period of maximal RAD2 mRNA accumulation during meiosis is consistent with a possible role of RAD2 in a late stage of recombination, in mismatch repair of heteroduplexes, or both.

Cell Cycle↗
PubMed1990

Pure red cell aplasia.

Eleven cases of Pure red cell aplasia (PRCA) in children were encountered in our hospital since 1982. The age range was 4 months to 12 years. There was a male preponderance with M:F ratio as 9:2. There were 4 cases due to viral fever, 1 with bronchopneumonia, 2 of tuberculosis, 1 of enteric, 1 of NHL and 2 were of congenital PRCA. Tuberculosis per-se had given rise to PRCA in the two cases, which is not reported earlier though its association with anti-tubercular therapy is well recorded. Cases of infective etiology other than viral responded very well to specific treatment. Steroid was the drug of choice in PRCA with viral etiology.

Child↗
PubMed1989

Interactions of the RAD7 and RAD23 excision repair genes of Saccharomyces cerevisiae with DNA repair genes in different epistasis groups.

The RAD7 and RAD23 genes of S. cerevisiae affect the efficiency of excision repair of UV-damaged DNA. We have examined the UV survival of strains carrying the rad7 and rad23 deletion mutation in combination with deletion mutations in genes affecting different DNA repair pathways. As expected, the rad7 delta and rad23 delta mutations interact epistatically with the excision repair defective rad1 delta mutation, and synergistically with the rad6 delta and rad52 delta mutations that affect the postreplication repair and recombinational repair pathways, respectively. However, the rad7 delta rad6 delta and the rad23 delta rad6 delta mutants exhibit the same level of UV sensitivity as the rad1 delta rad6 delta mutant. This observation is of interest since, in contrast to the rad7 delta or the rad23 delta mutations, the rad1 delta mutant is very UV sensitive and highly excision defective. This observation suggest that RAD6 and RAD7 and RAD23 genes complete for the same substrate during DNA repair.

DNA Repair↗
PubMed1989

Schistosomal egg granuloma-derived fibroblast-stimulating factor is apparently distinct from interleukin-1.

We have previously reported that egg granulomas isolated from livers of Schistosoma mansoni-infected euthymic mice in vitro elaborate a factor(s) that stimulates a variety of fibroblast responses including fibroblast proliferation and enhanced synthesis of extracellular matrix proteins. We have postulated that these factors play a role in the pathogenesis of hepatic fibrosis in schistosomiasis mansoni. Serum-free supernatants from egg granuloma cultures also stimulate thymocyte proliferation in an assay that defects interleukin-1 (IL-1). Thymocytes and fibroblasts are stimulated to proliferate by the same fractions of egg granuloma culture supernatant separated by gel filtration, isoelectric focusing, and ion-exchange chromatography. This suggested that granuloma-derived IL-1 is responsible for the observed fibroblast stimulation. Here we report that the ability of granuloma culture supernatants to stimulate the IL-1-sensitive D10.G4.1 cells but not fibroblasts is removed by treatment with immobilized anti-IL-1 antibody. We also observed that dialyzed culture supernatants from egg granulomas obtained from infected congenitally athymic (nude) mice also stimulate fibroblast proliferation. Treatment with anti-IL-1 antibody did not abrogate this response. In contrast to our experience with egg granulomas isolated from euthymic mice, IL-1- and fibroblast-stimulating activity could be separated by gel filtration and isoelectric focusing. We conclude that the fibroblast growth-stimulating activities elaborated by egg granulomas from S. mansoni-infected euthymic and athymic mice may be different but both appear to be distinct from IL-1.

Animals↗
PubMed1989

Conserved pattern of antisense overlapping transcription in the homologous human ERCC-1 and yeast RAD10 DNA repair gene regions.

We report that the genes for the homologous Saccharomyces cerevisiae RAD10 and human ERCC-1 DNA excision repair proteins harbor overlapping antisense transcription units in their 3' regions. Since naturally occurring antisense transcription is rare in S. cerevisiae and humans (this is the first example in human cells), our findings indicate that antisense transcription in the ERCC-1-RAD10 gene regions represents an evolutionarily conserved feature.

Base Sequence↗
PubMed1989

Cloning and sequence analysis of the Saccharomyces cerevisiae RAD9 gene and further evidence that its product is required for cell cycle arrest induced by DNA damage.

Procaryotic and eucaryotic cells possess mechanisms for arresting cell division in response to DNA damage. Eucaryotic cells arrest division in the G2 stage of the cell cycle, and various observations suggest that this arrest is necessary to ensure the completion of repair of damaged DNA before the entry of cells into mitosis. Here, we provide evidence that the Saccharomyces cerevisiae RAD9 gene, mutations of which confer sensitivity to DNA-damaging agents, is necessary for the cell cycle arrest phenomenon. Our studies with the rad9 delta mutation show that RAD9 plays a role in the cell cycle arrest of methyl methanesulfonate-treated cells and is absolutely required for the cell cycle arrest in the temperature-sensitive cdc9 mutant, which is defective in DNA ligase. At the restrictive temperature, cell cycle progression of cdc9 cells is blocked sometime after the DNA chain elongation step, whereas cdc9 rad9 delta cells do not arrest at this point and undergo one or two additional divisions. Upon transfer from the restrictive to the permissive temperature, a larger proportion of the cdc9 cells than of the cdc9 rad9 delta cells forms viable colonies, indicating that RAD9-mediated cell cycle arrest allows for proper ligation of DNA breaks before the entry of cells into mitosis. The rad9 delta mutation does not affect the frequency of spontaneous or UV-induced mutation and recombination, suggesting that RAD9 is not directly involved in mutagenic or recombinational repair processes. The RAD9 gene encodes a transcript of approximately 4.2 kilobases and a protein of 1,309 amino acids of Mr 148,412. We suggest that RAD9 may be involved in regulating the expression of genes required for the transition from G2 to mitosis.

Amino Acid Sequence↗
PubMed1989

Excision repair genes of Saccharomyces cerevisiae.

In the yeast Saccharomyces cerevisiae, at least ten genes are involved in excision repair of DNA damaged by UV radiation and by other agents that distort the DNA helix. Mutations in the RAD1, RAD2, RAD3, RAD4 and RAD10 genes render cells highly defective in the incision of damaged DNA, whereas mutations in the RAD7, RAD14, RAD16, RAD23 and MMS19 genes reduce the level of damage excision. This review summarizes the evidence for the involvement of these genes in excision repair and highlights the important features in the structures of the proteins encoded by the various RAD genes. The RAD3 protein has been purified and characterized in our laboratory, and it possesses single stranded DNA dependent ATPase and DNA helicase activities. The RAD3 helicase moves along the single-stranded DNA in the 5'----3' direction. We suggest that this activity plays a role in strand displacement synthesis during excision repair and in DNA replication.

DNA Repair↗
PubMed1988

Cloning and nucleotide sequence analysis of the Saccharomyces cerevisiae RAD4 gene required for excision repair of UV-damaged DNA.

The RAD4 gene of Saccharomyces cerevisiae is required for the incision step of excision repair. We have cloned the RAD4 gene and determined its nucleotide sequence. RAD4 encodes a somewhat basic protein of 754 amino acids (aa) with an Mr of 87,173. RAD4 contains several groups of 4-7 consecutive basic aa residues that could be involved in DNA binding and it also contains an alpha-helix-turn-alpha-helix motif for DNA binding. Like several other DNA repair proteins of S. cerevisiae, the C terminus of RAD4 protein is highly acidic.

Amino Acid Sequence↗
PubMed1988

Mutation of lysine-48 to arginine in the yeast RAD3 protein abolishes its ATPase and DNA helicase activities but not the ability to bind ATP.

The RAD3 gene of Saccharomyces cerevisiae is required for excision repair of DNA damaged by UV radiation and is also essential for cell viability. The approximately 89 kd protein encoded by RAD3 possesses single-stranded DNA dependent ATPase and DNA helicase activities. The sequence Gly-X-Gly-Lys-Thr, believed to be involved in the interaction with purine nucleotides in proteins that bind and hydrolyze the nucleotides, is present in the RAD3 primary structure between amino acids 45 and 49. We report here that the point mutation of Lys-48 to arginine abolishes the RAD3 ATPase and DNA helicase activities but not the ability to bind ATP. These observations highlight the involvement of this lysine residue in the hydrolysis of ATP and indicate that the positive charge on arginine can replace that of the lysine residue in the binding of ATP but not in its hydrolysis. The rad3 Arg-48 mutant is apparently defective in a step subsequent to incision at the damage site in DNA; it can incise UV damaged DNA, but does not remove pyrimidine dimers. The role of the ATPase and DNA helicase activities of the RAD3 protein in its DNA repair and viability functions is discussed.

Adenosine Triphosphatases↗