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Query: UNIPROT:P06889 (Mol)
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We had earlier characterized the nascent DNA synthesized in permeable cells of Bacillus subtilis in the presence of 5-mercurideoxycytidine triphosphate and 2',3'-dideoxyATP as being substituted at its 5' end with a ribonucleotide moiety of the sequence pApG(pC)1-2 DNA. In this paper, we examine the origin and turnover of the DNA-linked ribonucleotide and its relationship to DNA replication. At least 50% of the RNA-linked nascent DNA chains served as guanylate acceptors when incubated with GTP and the eukaryotic capping enzyme, indicating the presence of 5'-terminal di- or triphosphate groups and suggesting that the RNA moiety is synthesized de novo and is not a degradation product. In nascent DNA produced without limitation of chain growth by dideoxyATP, the degree of terminal ribonucleotide substitution was reduced by 50%, consistent with a linkage between RNA primer removal and DNA chain growth. Such a relationship was demonstrated directly by examining the RNA primer content of nascent DNA synthesized in the absence of dideoxyATP as a function of DNA chain length. As the DNA size increased from 40 to 200 nucleotide residues, the extent of RNA substitution declined from 80% to nearly 0%. Endgroup analysis showed that the loss of RNA was accompanied by a gradual shift from predominantly adenylate residues to 5'-terminal guanylate, consistent with a stepwise removal of ribonucleotides from the 5' end. Evidence that the nascent mercurated DNA synthesized under our experimental conditions was indeed a replicative intermediate came from the study of the time course of DNA chain growth and pulse-chase experiments. In the presence of the DNA ligase inhibitor NMN, mercurated DNA accumulated in two size classes with average length of approximately 750 and 8000 nucleotide residues, presumably representing the mature size of intermediates in discontinuous DNA synthesis. Comparison with the DNA size range at which the loss of the 5'-terminal RNA moiety occurred (40 to 200 residues) indicated that the processing of RNA primers occurred at an early stage during DNA chain elongation, and that moderate size intermediates in discontinuous DNA replication (greater than 200 nucleotides) have already lost their RNA primers.
J Mol Biol 1985 Nov 20
PMID:Origin and degradation of the RNA primers at the 5' termini of nascent DNA chains in Bacillus subtilis. 241 6

We have previously shown that Mu can sustain the growth at non-permissive temperature of an Escherichia coli strain harbouring a thermosensitive mutation in the DNA ligase structural gene. This "complementation" reaches a maximal level with the Mu lig3 mutant which restores the viability of a ligts7 strain to the level of the wild type (Ghelardini et al. 1980; Paolozzi et al. 1980). In this study we analysed the characteristics of this phenotypic suppression in order to clarify its molecular mechanism. We found that an E. coli ligts7 strain lysogenic for the Mu lig3 mutant shows: (i) an increment in the host DNA ligase activity; (ii) an increase in the specific mRNA of the host lig gene; (iii) an increase (towards the relaxed state) in the average linking number of a resident plasmid; and (iv) a reduction in DNA gyrase activity. These results are compatible with the hypothesis that the Mu lig gene product by interfering with the host enzymatic apparatus controlling DNA topology leads to a reduction in chromosomal supercoiling. The relaxation of the chromosome could affect the transcription of the DNA ligase gene, amongst others. Thus, through this mechanism, the Mu lig gene product is able to modulate gene expression and hence suppress the effects of the E. coli ligts7 mutation. On the basis of the identification of this mechanism of action, we propose to change the name of the Mu lig gene (thought originally to be the structural gene for a bacteriophage ligase) to gem (gene expression modulation).
Mol Gen Genet 1989 Mar
PMID:Suppression of the thermosensitive DNA ligase mutations in Escherichia coli K12 through modulation of gene expression induced by phage Mu. 254 6

Many genes of Escherichia coli have been shown to be sensitive to DNA superhelicity. The superhelicity of the chromosome is itself also supercoiling-dependent. We have developed a general strategy for investigating how a particular gene responds to changes in DNA topology. This approach is used to study the E. coli ligase gene. The thermosensitivity of the E. coli ligts251 mutation can be phenotypically suppressed by mutations which map close to, or in, the gyrB gene and which affect the degree of DNA supercoiling. The level of suppression correlates with the degree of DNA relaxation observed, suggesting that the gene encoding the E. coli DNA ligase is activated by relaxation of the chromosomal DNA.
Mol Microbiol 1989 Mar
PMID:The expression of the DNA ligase gene of Escherichia coli is stimulated by relaxation of chromosomal supercoiling. 254 2

DNA sequence analysis of genetic deletions in bacteriophage T7 has shown that these chromosomal rearrangements frequently occur between directly repeated DNA sequences. To study this type of spontaneous deletion in more quantitative detail synthetic fragments of DNA, made by hybridizing two complementary oligonucleotides, were introduced into the non-essential T7 gene 1.3 which codes for T7 DNA ligase. This insert blocked synthesis of functional ligase and made the phage that carried an insert unable to form plaques on a host strain deficient in bacterial ligase. The sequence of the insert was designed so that after it is put into the T7 genome the insert is bracketed by direct repeats. Perfect deletion of the insert between the directly repeated sequences results in a wild-type phage. It was found that these deletion events are highly sensitive to the length of the direct repeats at their ends. In the case of 5 bp direct repeats excision from the genome occurred at a frequency of less than 10(-10), while this value for an almost identical insert bracketed by 10 bp direct repeats was approximately 10(-6). The deletion events were independent of a host recA mutation.
Mol Gen Genet 1989 Jun
PMID:Genetic deletions between directly repeated sequences in bacteriophage T7. 254 73

We have previously shown that the inhibition of MNU-induced DNA repair by arsenite occurs after the incision step in Chinese hamster V79 cells. We now report that nuclear DNA ligase activity is inhibited after arsenite treatment and that the inhibited activity is mostly DNA ligase II. Both constitutive and MNU-inducible levels of DNA ligase II are inhibited. The addition of arsenite in vitro also indicates that DNA ligase II is more sensitive to arsenite inhibition than DNA ligase I. Since DNA ligase II is reported to be involved in the ligation step of excision repair, its inhibition by arsenite is a likely mechanism for the inhibition of DNA repair by arsenite and may account for the fact that arsenite acts as a comutagen with a number of different types of mutagens. The carcinogenicity of arsenite may also be a result of ligase inhibition.
Mol Toxicol 1989
PMID:Inhibition of DNA ligase activity by arsenite: a possible mechanism of its comutagenesis. 261 68

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.
Mol Cell Biol 1989 May
PMID: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. 266 61

Numerous DNA-interactive proteins have been shown to locate specific sequences within large domains of non-target DNA in vitro and in vivo by a one-dimensional diffusion mechanism; however, the biological significance of this process has not been evaluated. We have examined the biological consequences of sliding for the pyrimidine dimer-specific DNA repair enzyme T4 endonuclease V, an enzyme which scans non-target DNA both in vitro and in vivo. An endonuclease V mutant was constructed whose only altered biochemical characteristic, measured in vitro, was a loss in its ability to slide on non-target DNA. In contrast to the native enzyme, when the mutated endonuclease V was expressed in DNA repair-deficient Escherichia coli, no enhanced ultraviolet survival was conferred. These results suggest that the mechanisms which DNA-interactive proteins employ to enhance the probability of locating their target sequences are of significant biological importance.
J Mol Biol 1989 Aug 20
PMID:Biological consequences of a reduction in the non-target DNA scanning capacity of a DNA repair enzyme. 268 89

The DNA homology and adsorption specificity of newly isolated virulent bacteriophages of P. aeruginosa have been studied. On the basis of this analysis all phages were divided into four groups: phi k, phi m, phi mnP78-like and phi mnF82-like bacteriophages. DNA's of phi k as well as phi m phages were shown to possess different restriction patterns although they have an extensive homology. Unlike other groups, phi k phages were characterized by the presence of T4 DNA ligase--repaired, single-chain breaks.
Mol Gen Genet 1985
PMID:DNA homology and adsorption specificity of Pseudomonas aeruginosa virulent bacteriophages. 299 7

The DNA ligase of Escherichia coli catalyses the NAD-dependent formation of phosphodiester linkages between 5'-phosphoryl and 3'-hydroxyl groups in DNA. It is essential for DNA replication and repair of damaged DNA strands. We determined the nucleotide sequence of the lig gene of Escherichia coli coding for DNA ligase and flanking regions. The coding frame of the gene was confirmed by the amino acid composition and the amino- and carboxyl-terminal amino acid sequences of the purified ligase. The ligase consists of 671 amino acid residues with a molecular weight of 73,690.
Mol Gen Genet 1986 Jul
PMID:Nucleotide sequence of the lig gene and primary structure of DNA ligase of Escherichia coli. 301 36

It was shown that bacteriophage tf as well as bacteriophages phi p4/40, phi p25/42, phi p23/40 and phi p6/40, which are specific to different P. putida strains, contain the single strand breaks in their DNA. The breaks are localized in one strand of DNA molecules and are repairable with T4 DNA ligase. Bacteriophage tf has no detectable DNA homology with phi p4/40, phi p25/42, phi p23/40 and phi p6/40 bacteriophages. All the phages studied have no relation with other known Pseudomonas phages. Bacteriophages phi p4/40 and phi p25/42 share the extensive DNA homology.
Mol Gen Mikrobiol Virusol 1988 May
PMID:[Bacteriophages of Pseudomonas putida containing single-stranded canonical DNA breaks]. 313 62


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