Enzymatic synthesis of deoxyribonucleic acid. xiv. further purification and properties of deoxyribonucleic acid polymerase of escherichia coli.

Phage T4 has provided countless contributions to the paradigms of genetics and biochemistry. Its complete genome sequence of 168,903 bp encodes about 300 gene products. T4 biology and its genomic sequence provide the best-understood model for modern functional genomics and proteomics. Variations on gene expression, including overlapping genes, internal translation initiation, spliced genes, translational bypassing, and RNA processing, alert us to the caveats of purely computational methods. The T4 transcriptional pattern reflects its dependence on the host RNA polymerase and the use of phage-encoded proteins that sequentially modify RNA polymerase; transcriptional activator proteins, a phage sigma factor, anti-sigma, and sigma decoy proteins also act to specify early, middle, and late promoter recognition. Posttranscriptional controls by T4 provide excellent systems for the study of RNA-dependent processes, particularly at the structural level. The redundancy of DNA replication and recombination systems of T4 reveals how phage and other genomes are stably replicated and repaired in different environments, providing insight into genome evolution and adaptations to new hosts and growth environments. Moreover, genomic sequence analysis has provided new insights into tail fiber variation, lysis, gene duplications, and membrane localization of proteins, while high-resolution structural determination of the "cell-puncturing device," combined with the three-dimensional image reconstruction of the baseplate, has revealed the mechanism of penetration during infection. Despite these advances, nearly 130 potential T4 genes remain uncharacterized. Current phage-sequencing initiatives are now revealing the similarities and differences among members of the T4 family, including those that infect bacteria other than Escherichia coli. T4 functional genomics will aid in the interpretation of these newly sequenced T4-related genomes and in broadening our understanding of the complex evolution and ecology of phages-the most abundant and among the most ancient biological entities on Earth.

Bacteriophage T4 Genome

We used mice deficient in each of the eight types and subtypes of prostanoid receptors and examined the roles of prostanoids in dextran sodium sulfate–induced (DSS-induced) colitis. Among the prostanoid receptor–deficient mice, only EP4-deficient mice and not mice deficient in either DP, EP1, EP2, EP3, FP, IP, or TP developed severe colitis with 3% DSS treatment, which induced only marginal colitis in wild-type mice. This phenotype was mimicked in wild-type mice by administration of an EP4-selective antagonist (AE3-208). The EP4 deficiency impaired mucosal barrier function and induced epithelial loss, crypt damage, and aggregation of neutrophils and lymphocytes in the colon. Conversely, administration of an EP4-selective agonist (AE1-734) to wild-type mice ameliorated severe colitis normally induced with 7% DSS, while that of AE3-208 suppressed recovery from colitis and induced significant proliferation of CD4+ T cells. In vitro AE3-208 enhanced and AE1-734 suppressed the proliferation and Th1 cytokine production of lamina propria mononuclear cells from the colon. DNA microarray analysis revealed elevated expression of genes associated with immune response and reduced expression of genes with mucosal repair and remodeling in the colon of EP4-deficient mice. We conclude that EP4 maintains intestinal homeostasis by keeping mucosal integrity and downregulating immune response.

/pdf/the-prostaglandin-receptor-ep4-suppresses-colitis-mucosal-1qxwghzmuz.pdf

The prostaglandin receptor EP4 suppresses colitis, mucosal damage and CD4 cell activation in the gut

https://www.jbc.org/content/245/1/39.full.pdf

Enzymatic synthesis of deoxyribonucleic acid. XXXII. Replication of duplex deoxyribonucleic acid by polymerase at a single strand break.

Homozygous xeroderma pigmentosum fibroblasts cannot repair damage to DNA bases, but can repair damage that involves chain breaks. In xeroderma pigmentosum, therefore, there is a defect in an early step in repair at which base damage is recognized and the polynucleotide chain broken enzymatically (by an endonuclease). Heterozygous fibroblasts repair base damage to normal extents. Carcinogenesis in xeroderma pigmentosum, and perhaps in some normal individuals, may be the result of somatic mutations caused by unrepaired damage.

Xeroderma pigmentosum: a human disease in which an initial stage of dna repair is defective

Mechanism of repair of DNA in bacteriophage: I. Excision of pyrimidine dimers from ultraviolet-irradiated DNA by an extract of T4-infected cells☆

Nucleases specific for ultraviolet light-irradiated DNA and their possible role in dark repair.

A mutant of Micrococcus lysodeikticus defective in a deoxyribonuclease activity specific for ultraviolet-irradiated DNA

A deoxyribonuclease activity specific for ultraviolet-irradiated DNA: A chromatographic analysis

Suppressor-sensitive mutants of Bacillus subtilis phage SPO2 were isolated and classified into 18 cistrons. A linear genetic map was constructed. The genes controlling early functions of phage development were clustered near the CI gene which may produce phage repressor.

Shunzo Okubo

Papers

Mechanism of repair of DNA in bacteriophage: I. Excision of pyrimidine dimers from ultraviolet-irradiated DNA by an extract of T4-infected cells☆

Nucleases specific for ultraviolet light-irradiated DNA and their possible role in dark repair.

A mutant of Micrococcus lysodeikticus defective in a deoxyribonuclease activity specific for ultraviolet-irradiated DNA

A deoxyribonuclease activity specific for ultraviolet-irradiated DNA: A chromatographic analysis

Isolation and Properties of Suppressor-Sensitive Mutants of Bacillus subtilis Bacteriophage SPO2