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)

During digestion of deoxyribonucleoproteins (DNP) of gram-negative bacteria by micrococcal nuclease and Ca2+, Mg2+-dependent endonuclease in situ regular series fragments-and large nuclease-resistent fragments of DNP were revealed by electrophoresis. The DNP length of the smallest DNP-fragment was tentatively 120-140 base pairs. In investigated bacterial species DNP contained at least two basic proteins which had electrophoretic mobility similar to that of histone H4 of eucaryot. It is suggested that bacterial DNPs have common regular structure.
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PMID:[Probing the structure of bacterial deoxyribonucleoproteins with exogenous and endogenous nucleases]. 624 43

Histone acetylation, DNA replicative synthesis, UV-induced DNA repair synthesis, and UV-induced endonuclease-sensitive sites were measured in normal human fibroblasts and xeroderma pigmentosum fibroblasts (complementation groups A, C, and D) following exposure to sodium butyrate. In all four cell types, treatment with millimolar concentrations of sodium butyrate resulted in a hyperacetylation of the core histones. Furthermore, following an exposure of 20 mM sodium butyrate for 48 h, the extent of hyperacetylation was the same in each cell type. In agreement with previous reports, we observed a marked decrease in DNA replicative synthesis in each cell type following increasing times of exposure to sodium butyrate. On the other hand, we observed a marked increase in DNA repair synthesis occurring during early times after UV irradiation in normal cells and in two of the xeroderma pigmentosum cell strains (groups C and D). This increase appeared to correlate with the increase in the highest acetylated form of histone H4. Furthermore, the total number of endonuclease-sensitive sites (i.e. prior to the onset of repair) induced by UV radiation was the same in both butyrated-treated and untreated normal cells over the dose range of 0-20 J/m2. However, the initial rate of removal of these sites increased in butyrate-treated normal cells. These results indicate that sodium butyrate stimulates the initial rate of nucleotide excision repair in both normal and (partially) repair-deficient human cells at concentrations where the histones are maximally hyperacetylated.
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PMID:Sodium butyrate stimulates DNA repair in UV-irradiated normal and xeroderma pigmentosum human fibroblasts. 714 58

To study whether the acetylation of one or more of the four acetylatable lysines of histone H4 affects its binding to DNA, we have designed a protection experiment with a model system consisting in phage lambda DNA as substrate, StuI as restriction endonuclease and histone H4 with different degrees of acetylation as the protective agent. It can be deduced from the experimental data that the protection afforded by the histone is not dependent on the number of positive charges lost by acetylation. Thus, non-acetylated H4 and mono-acetylated H4 cause similar protection, while di-acetylation of the histone seems to be the crucial step in significantly weakening the interaction between H4 and DNA. This is confirmed by the results obtained in protection experiments carried out using H4 peptide (1-24) with different degrees of acetylation as the protecting agent. As restriction enzyme can imitate any trans-acting factor with sequence recognition, the di-acetylated isoform of histone H4 can be the starting point, through acetylation, to unmask DNA sequences, allowing the accessibility of regulatory factors to DNA in the chromatin.
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PMID:Interaction between N-terminal domain of H4 and DNA is regulated by the acetylation degree. 954 42

Genetic studies have suggested that chromatin structure is involved in repression of the silent mating type loci in Saccharomyces cerevisiae. Chromatin mapping at nucleotide resolution of the transcriptionally silent HMLalpha and the active MATalpha shows that unique organized chromatin structure characterizes the silent state of HMLalpha. Precisely positioned nucleosomes abutting the silencers extend over the alpha1 and alpha2 coding regions. The HO endonuclease recognition site, nuclease hypersensitive at MATalpha, is protected at HMLalpha. Although two precisely positioned nucleosomes incorporate transcription start sites at HMLalpha, the promoter region of the alpha1 and alpha2 genes is nucleosome free and more nuclease sensitive in the repressed than in the transcribed locus. Mutations in genes essential for HML silencing disrupt the nucleosome array near HML-I but not in the vicinity of HML-E, which is closer to the telomere of chromosome III. At the promoter and the HO site, the structure of HMLalpha in Sir protein and histone H4 N-terminal deletion mutants is identical to that of the transcriptionally active MATalpha. The discontinuous chromatin structure of HMLalpha contrasts with the continuous array of nucleosomes found at repressed a-cell-specific genes and the recombination enhancer. Punctuation at HMLalpha may be necessary for higher-order structure or karyoskeleton interactions. The unique chromatin architecture of HMLalpha may relate to the combined requirements of transcriptional repression and recombinational competence.
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PMID:High-resolution structural analysis of chromatin at specific loci: Saccharomyces cerevisiae silent mating type locus HMLalpha. 971 Jun 23

Previously, we have shown that breakpoints induced by the endonucleases AluI, BamHI and DNase I in CHO chromosomes are localized mainly in G-light bands. Neutrons and gamma rays produced similar breakpoint clusters to endonucleases in most CHO chromosomes. Here we compare endonuclease- and radiation-induced breakpoint maps with hyperacetylation patterns of histone H4. The H4 acetylation pattern in chromosomes is similar to the pattern of G-light, or R-bands, and breakpoints are clustered in highly acetylated chromosome regions. These findings indicate that chromosomal aberrations occur more frequently in active than in inactive chromatin.
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PMID:Chromosome regions enriched in hyperacetylated histone H4 are preferred sites for endonuclease- and radiation-induced breakpoints. 1127 94

SV40 chromosomes undergoing encapsidation late in infection and SV40 chromatin in virions are hyperacetylated on histones H4 and H3. However, the fate of the SV40 chromosomes containing hyperacetylated histones in a subsequent round of infection has not been determined. In order to determine if SV40 chromosomes undergo changes in the extent of histone acetylation during early infection, we have analyzed SV40 chromosomes isolated 30 min and 3 h postinfection by quantitative ChIP assays, depletion ChIP assays, competitive ChIP assays, and ChIP assays combined with restriction endonuclease sensitivity using antibodies to hyperacetylated histones H4 and H3. We have shown that at 30 min postinfection, the hyperacetylated histones are associated with two distinct classes of SV40 chromosomes. One form is hyperacetylated specifically on histone H4 while a second form is hyperacetylated on both H4 and H3. Both forms of chromosomes appear to contain a nucleosome-free promoter region. Over the course of the next few hours of infection, the class of SV40 chromosomes hyperacetylated on only H4 is reduced or completely eliminated through deacetylation.
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PMID:Hyperacetylation and differential deacetylation of histones H4 and H3 define two distinct classes of acetylated SV40 chromosomes early in infection. 1498 Apr 92

Distinct patterns of posttranslational histone modifications can regulate DNA-templated events such as mitosis, transcription, replication, apoptosis, and DNA damage, suggesting the presence of a "histone code" in these nuclear processes. Phosphorylation of histone H2A S129 at sites of DNA double-strand breaks (DSBs) has been implicated in damage repair in yeast. Here, we describe another phosphorylation event on serine 1 (S1) of histone H4; this event is also associated with MMS- or phleomycin-induced DSBs but not with UV-induced DNA damage. Chromatin-immunoprecipitation (ChIP) studies of an HO-endonuclease-inducible strain show that S1 phosphorylation is specifically enhanced 20- to 25-fold in nucleosomes proximal to the DSB. In addition, we show that casein kinase II (CK2) can phosphorylate H4 S1 in vitro and that null or temperature-sensitive CK2 yeast mutants are defective for induction of H4 S1 phosphorylation upon DNA damage in vivo. Furthermore, H4 S1 phosphorylation and CK2 play a role in DSB re-joining as indicated by a nonhomologous end-joining (NHEJ) plasmid assay. CK2 has been implicated in regulating a DNA-damage response; our data suggest that histone H4 S1 is one of its physiological substrates. These data suggest that this modification is a part of the DNA-repair histone code.
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PMID:Phosphorylation of histone H4 serine 1 during DNA damage requires casein kinase II in S. cerevisiae. 1582 38

Type B histone acetyltransferases are thought to catalyze the acetylation of the NH(2)-terminal tails of newly synthesized histones. Although Hat1p has been implicated in cellular processes, such as telomeric silencing and DNA damage repair, the underlying molecular mechanisms by which it functions remain elusive. In an effort to understand how Hat1p is involved in the process of DNA double-strand break (DSB) repair, we examined whether Hat1p is directly recruited to sites of DNA damage. Following induction of the endonuclease HO, which generates a single DNA DSB at the MAT locus, we found that Hat1p becomes associated with chromatin near the site of DNA damage. The nuclear Hat1p-associated histone chaperone Hif1p is also recruited to an HO-induced DSB with a similar distribution. In addition, while the acetylation of all four histone H4 NH(2)-terminal tail domain lysine residues is increased following DSB formation, only the acetylation of H4 lysine 12, the primary target of Hat1p activity, is dependent on the presence of Hat1p. Kinetic analysis of Hat1p localization indicates that it is recruited after the phosphorylation of histone H2A S129 and concomitant with the recombinational-repair factor Rad52p. Surprisingly, Hat1p is still recruited to chromatin in strains that cannot repair an HO-induced double-strand break. These results indicate that Hat1p plays a direct role in DNA damage repair and is responsible for specific changes in histone modification that occur during the course of recombinational DNA repair.
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PMID:Recruitment of the type B histone acetyltransferase Hat1p to chromatin is linked to DNA double-strand breaks. 1661 3

Histone acetylation/deacetylation constitute the most relevant chromatin remodelling mechanism to control DNA access to nuclear machinery as well as to mutagenic agents. Thus, these epigenetics mechanisms could be involved in processing DNA lesions into chromosomal aberrations. Although radiation-induced DNA lesions are believed to occur randomly, in most cases chromosome breakpoints appear distributed in a non-random manner. In order to study the distribution of chromosome damage induced by clastogenic agents in relation to chromosome histone acetylation patterns, an experimental model based on treating Chinese hamster cells with endonucleases and ionizing radiations as well as immunolabelling metaphase chromosomes with antibodies to acetylated histone H4 was developed. The analysis of intra- and interchromosome breakpoint distribution has been carried out on G-banded chromosomes, and results obtained were correlated with chromosome acetylated histone H4 profiles. A co-localization of intrachromosomal breakpoints induced by Alu I, Barn HI and DNase I as well as by neutrons and gamma-rays was observed. Radiation- and endonuclease-induced breakpoints tend to cluster in less condensed chromosome regions (G-light bands) that show the highest levels of acetylated histone H4. The analysis of interchromosomal distribution of radiation-induced lesions showed a concentration ofbreakpoints in Chinese hamster chromosomes with particular histone acetylation patterns. The fact that chromosome break-points occur more frequently in transcriptionally competent chromosome regions suggests that chromatin conformation and nuclear architecture could play a role in the distribution of chromosome lesions.
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PMID:Chromatin remodelling and chromosome damage distribution. 1701 7