Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.30.2 (endonuclease)
 18,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A high mobility group (HMG) nonhistone protein fraction HMG(1 + 2), composed of HMG1 and HMG2, was prepared from pig thymus chromatin. In order to examine a possibility that the HMG(1 + 2) participates in the unwinding of the DNA double-helix, DNA hydrolysis assay systems with the endonucleases specific for single-stranded DNA were employed. In the presence of HMG(1 + 2), the hydrolysis of double-stranded DNA by N. crassa endonuclease was markedly promoted, while the hydrolysis of single-stranded DNA was hardly enhanced. The reaction kinetic data showed that the stimulation of the hydrolysis of double-stranded DNA in the presence of HMG(1 + 2) was due to the unwinding of the DNA double-helix by the HMG(1 + 2), and not due to stimulation of enzyme activity of the endonuclease by the protein. The unwinding reactions were dependent on the HMG protein concentration at low weight protein to DNA ratios and reached a maximum at the ratio of 0.025. The region unwound in the whole DNA was partial. Similar results were obtained for experiments with nuclease S1. Isolated HMG1 and HMG2 fractions showed DNA unwinding activity of similar extents. The association constant obtained by fluorescence quenching analysis showed that the HMG(1 + 2) has higher affinity to single-stranded DNA than to double-stranded DNA. The susceptibility to the unwinding differed with the DNA source. These results suggest that HMG(1 + 2) at a low weight protein to DNA ratio binds to some limited double-stranded region in DNA and unwinds the DNA partially.
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PMID:Unwinding of DNA by nonhistone chromosomal protein HMG(1 + 2) from pig thymus as determined with endonuclease. 632 90

Rolling-circle replication is initiated by a replicon-encoded endonuclease which introduces a single-strand nick into specific origin sequences, becoming covalently attached to the 5' end of the DNA at the nick and providing a 3' hydroxyl to prime unidirectional, leading-strand synthesis. Parvoviruses, such as minute virus of mice (MVM), have adapted this mechanism to amplify their linear single-stranded genomes by using hairpin telomeres which sequentially unfold and refold to shuttle the replication fork back and forth along the genome, creating a continuous, multimeric DNA strand. The viral initiator protein, NS1, then excises individual genomes from this continuum by nicking and reinitiating synthesis at specific origins present within the hairpin sequences. Using in vitro assays to study ATP-dependent initiation within the right-hand (5') MVM hairpin, we have characterized a HeLa cell factor which is absolutely required to allow NS1 to nick this origin. Unlike parvovirus initiation factor (PIF), the cellular complex which activates NS1 endonuclease activity at the left-hand (3') viral origin, the host factor which activates the right-hand hairpin elutes from phosphocellulose in high salt, has a molecular mass of around 25 kDa, and appears to bind preferentially to structured DNA, suggesting that it might be a member of the high-mobility group 1/2 (HMG1/2) protein family. This prediction was confirmed by showing that purified calf thymus HMG1 and recombinant human HMG1 or murine HMG2 could each substitute for the HeLa factor, activating the NS1 endonuclease in an origin-specific nicking reaction.
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PMID:High-mobility group 1/2 proteins are essential for initiating rolling-circle-type DNA replication at a parvovirus hairpin origin. 976 84

Granzyme A, a serine protease in the cytotoxic granules of natural killer cells and cytotoxic T lymphocytes, induces caspase-independent cell death when introduced into target cells by perforin. Granzyme A induces single-stranded DNA damage as well as rapid loss of cell membrane integrity and mitochondrial transmembrane potential through unknown mechanisms. Granzyme A destroys the nuclear envelope by targeting lamins and opens up DNA for degradation by targeting histones. A special target of the granzyme A cell death pathway is an endoplasmic reticulum-associated complex, called the SET complex, which contains three granzyme A substrates, the nucleosome assembly protein SET, the DNA bending protein HMG-2, and the base excision repair endonuclease Ape1. The SET complex also contains the tumor suppressor protein pp32 and the granzyme A-activated DNase NM23-H1, which is inhibited by SET. Granzyme A cleavage of SET releases the inhibition and unleashes NM23-H1. Cleavage of Ape1 by granzyme A interferes with the ability of the target cell to repair itself. The novel cell death pathway initiated by granzyme A provides a parallel pathway for apoptosis, important in destroying targets that overexpress bcl-2 or are otherwise invulnerable to the caspases.
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PMID:Nuclear war: the granzyme A-bomb. 1449 64