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

Calf thymus DNA and M13mp9 RF DNA were modified with [ring-3H]2-naphthyl isocyanate (NIC) and analyzed by reverse-phase HPLC following enzymatic hydrolysis. In each case, essentially, a single radioactive component, which co-chromatographed with authentic N4-2-naphthyl-carbamoyl-2'-deoxycytidine (NCdC), was detected. In order to explore the biological potential of this adduct, mp9 RF DNA modified with NIC was introduced into Escherichia coli strains using a calcium chloride technique. The plaque-forming efficiencies of DNA decreased with increasing adduct level, and the decreases were more pronounced in Uvr endonuclease-deficient strains (i.e. AB1886, uvrA; AB1885, uvrB; AB1884, uvrC) as compared to JM103 (Uvr endonuclease proficient) and JM101 RH03 (recA). These results suggest that these lesions, NCdC adducts, can be removed by the Uvr endonuclease repair system. Mutations were detected as the loss of ability of the bacteriophage to complement the defective beta-galactosidase of the host cells. Induction of SOS functions in the host cells enhanced the mutation frequency to 0.089%, i.e. greater than or equal to 4-fold greater than in non-SOS-induced cells, in transfections with RF DNA that contained 100 adducts/molecule. The mutagenic potency of this cytidine lesion is lower than that of the guanine-C8 adducts of 2-aminofluorene and 2-acetylaminofluorene as reported previously for this mutagenesis system.
Carcinogenesis 1990 Nov
PMID:Characterization and genotoxicity of DNA adducts caused by 2-naphthyl isocyanate. 222 33

Cells from patients with the cancer-prone inherited disease, xeroderma pigmentosum (XP) are known to be defective in the endonuclease-mediated incision step in excision repair of a number of different types of DNA adducts, but the molecular events responsible have not been delineated. We have previously reported isolation of two DNA endonucleases, pI 4.6 and 7.6, from normal human chromatin which recognize adducts produced by psoralen plus long wavelength ultraviolet radiation (UVA). These endonucleases are both present in XP complementation group A (XPA) cells even though these cells are hypersensitive to this type of damage. We now report that introduction by electroporation of either normal endonuclease into XPA cells restored their markedly deficient DNA repair-related unscheduled DNA synthesis (UDS) to higher than normal levels following exposure to psoralen plus UVA. Introduction of XPA endonucleases into similarly treated XPA cells had little or no restorative effect on UDS. However, both normal and XPA endonucleases increased UDS in normal cells to higher than normal levels. These results indicate that XPA cells have endonucleases which can repair these adducts but which cannot function in intact cells unless a factor(s), which they lack is provided by normal cells.
Carcinogenesis 1990 Mar
PMID:Electroporation of normal human DNA endonucleases into xeroderma pigmentosum cells corrects their DNA repair defect. 231 Nov 96

We examined the methylation pattern and organization of the AFP gene in whole livers and in isolated cell populations purified from livers of rats fed a carcinogenic diet which interferes with DNA methylation. Using restriction endonuclease digestion, we find no differences in methylation pattern and overall organization of the AFP gene in oval cells (AFP-producers) and hepatocytes (non-producers) isolated at the early stages of carcinogenesis. Our studies indicate that in cell populations which produce AFP as well as in cells which are not active in AFP synthesis, the majority of the CCGG sites of the AFP gene are extensively methylated. In addition, we describe the existence of polymorphism in the AFP and albumin genes of Sprague-Dawley rats.
 ...
PMID:Methylation of the alphafetoprotein gene in cell populations isolated from rat livers during carcinogenesis. 241 27

Apurinic/apyrimidinic (AP) sites were measured in HeLa cells by digestion of cellular DNA with Escherichia coli endonuclease IV, an AP-specific endonuclease, prior to alkaline elution. The absence of non-specific endonuclease activity allowed endonuclease IV-sensitive AP sites to be detected with the sensitivity of conventional alkaline elution. Cells that were alkylated with dimethyl sulfate contained AP sites that were repaired along with DNA single-strand breaks during a post-alkylation recovery period. These results show that DNA alkylation products are repaired, at least in part, via an AP intermediate suggesting a repair pathway initiated by DNA glycosylases followed by DNA incision by AP endonuclease.
Carcinogenesis 1986 Jul
PMID:DNA repair pathway in alkylated human cells: apurinic/apyrimidinic intermediate resolved by Escherichia coli endonuclease IV-coupled alkaline elution. 242 29

We have developed a new assay which allows us to monitor the rates of repair of potentially lethal damage in u.v. (254 nm)-irradiated normal human skin fibroblasts. Using this assay we have shown that, in non-dividing cells, the majority of biologically effective excision repair is completed within 4 h following irradiation with low fluences of u.v. (1.5-6.0 J/m2). During this time, non-dividing cells removed only approximately 20% of the pyrimidine dimers induced in DNA by a u.v. fluence of 3.0 J/m2 as measured by the loss of u.v.-endonuclease-sensitive sites under identical repair conditions. The rates of repair of potentially lethal damage were also found to be independent of u.v. fluence over the range 1.5-6.0 J/m2 in non-dividing cells. In contrast, in cells irradiated in exponential growth with 1.5 J/m2, the rate of biologically effective repair was comparable with that observed in non-dividing cells but the efficiency of the repair process declined progressively with increase in u.v. fluence from 1.5 to 6.0 J/m2. Our data support the concept that the biological recovery of u.v.-irradiated cells depends on the preferential repair of damage in functionally important domains in the genome.
Carcinogenesis 1987 Sep
PMID:Rapidly occurring DNA excision repair events determine the biological expression of u.v.-induced damage in human cells. 244 87

There seems to be a current view that the inhibition of DNA methylation may be a mechanism of initiation of carcinogenesis or one of the steps required in the carcinogenic process. However, because of the deficiencies in research works on cellular level, there is a long way to make such a general relationship between carcinogen and the inhibition of cellular DNA methylation. In this paper the effects of some chemical carcinogens on methylation of newly replicated DNA in human FL cells was analyzed by comparing the weight average length (Lw) of the DNA digests after complete digestion by restriction endonuclease Hpa II. It was observed that two non-genotoxic carcinogens (5-azacytidine and L-ethionine) and two genotoxic carcinogens (MNNG and aflatoxin B1) used in this study all caused obvious cytotoxicity on FL cells at the test concentration. Five days after the termination of 5-azacytidine treatment (2 x 10(-6) M, 24 hours), Lw (kb) of the Hpa II digests of cellular DNA was smaller than that of control (8.0 +/- 0.1 vs 10.9 +/- 1.0, P less than 0.01), the Lw change rate was -27%. When DNA was analyzed from FL cells after 9 days continuous treatment of L-ethionine (2 x 10 M), the digestibility of Hpa II was also increased as compared with that of the control, the Lw values (kb) showed a decrease of about 8% (9.8 +/- 0.3 vs 10.6 +/- 0.3, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Is hypomethylation of cellular DNA a step required in the initiation process of chemical carcinogenesis?]. 248 41

The polymerase chain reaction (PCR) is a rapid method for generating a 10(6)- to 10(7)-fold increase in the number of copies of a discrete DNA or RNA sequence. The technique is being used for rapid prenatal diagnosis and carrier testing of several inherited disorders. After PCR, mutations producing single-gene disorders can be detected by several different methods, including endonuclease digestion and gel electrophoresis (applicable when a mutation affects an endonuclease recognition site), gel electrophoresis (used for detection of deletions), and hybridization to an oligonucleotide probe specific for a mutation. Less often, gene sequencing of a PCR product is used to rapidly identify a mutation. In addition, the PCR technique can be applied to polymorphism analysis to provide diagnosis by linkage analysis. In other areas, PCR is being used to detect and characterize microbial pathogens and to characterize mutations associated with carcinogenesis. The PCR method is useful in situations in which the amount of DNA sample is limited, such as in forensics and prenatal testing, or in which the quality of the DNA sample is poor.
 ...
PMID:Use of polymerase chain reaction for diagnosis of inherited disorders. 257 Jun 52

Chromosome 5 allele loss is a genetic alteration occurring during the multistep progression of colon carcinogenesis. To determine whether a similar genetic alteration occurs in other gastrointestinal malignancies, the authors have analyzed DNA extracted from freshly frozen normal and neoplastic tissue from nineteen patients who underwent radical resections for gastric, ampullary and pancreatic adenocarcinomas at the University of Chicago. Loss of heterozygosity for alleles on the long arm of chromosome 5 was detected in tumor DNA compared to normal tissue DNA from the same patient using restriction fragment length polymorphisms (RFLPs). Eleven patients were informative using the restriction endonuclease TaqI to generate RFLPs for chromosome 5 probes C11 P11 and pTP5E. Loss of heterozygosity was found in one of eight informative gastric carcinomas (12.5%) and in one of two informative ampullary carcinomas. The only informative pancreatic adenocarcinoma was heterozygous. It is concluded that chromosome 5 allele loss occurs in a variety of gastrointestinal malignancies and suggest that common genetic origins may underlie these different tumors.
 ...
PMID:Chromosome 5 allele loss in human gastric, ampullary and pancreatic carcinomas. 257 24

Mutagenesis, clastogenesis, and carcinogenesis, may all be S-phase dependent processes within carcinogen-damaged human cells. Carcinogens have been shown to inhibit replicative DNA synthesis in S phase cells and the mechanisms of inhibition have been identified. It is proposed that the sequelae of carcinogen action (mutations, sister-chromatid exchanges, chromosome aberrations) are the consequence of the production of lesions in the DNA template which interfere with the ability of DNA polymerase to synthesize a complementary strand without error. Mis-instructive lesions in the template give rise to base-substitution mutations in nascent strands as DNA polymerase inserts an incorrect but complementary base. Non-instructive base lesions and sterically interfering bulky adducts in the template inhibit DNA polymerase and cause the growing points of nascent DNA strands to be blocked. This blockage perpetuates discontinuities in daughter strands. These discontinuities are eliminated by a process known as post-replication repair. Blocked growing points may be relieved by un-directed insertion of DNA precursors to span the non-instructive lesions. Transient dislocation of the primer terminus from the damaged template may occur at palindromic or repetitive sequences. Reannealing of the primer terminus beyond the site of damage may allow bypass of blocking lesions with a consequence of deletion or insertion of genetic information. DNA at the site of blocked growing points may be a substrate for other enzymes involved in DNA metabolism. Single-strand gaps in daughter strands may be recognized by Rec A-like proteins which catalyze paranemic invasion of sister duplex strands. Recombination intermediates generated at sites of blocked growing points may be resolved by a pathway that produces either sister-chromatid exchanges or the insertion of a patch of parental template DNA within the daughter strand. Single-strand-specific endonuclease may attack regions of denatured DNA at blocked growing points producing double-strand breaks which appear to be intermediates in the formation of chromatid aberrations. The utilization of each of these pathways of post-replication repair will depend upon the precise structure of the template lesion, the sequence context in which the lesion is embedded in the template strand, and stochastic processes.
Carcinogenesis 1989 Jan
PMID:Pathways of human cell post-replication repair. 264 48

The specific recognition of various DNA modifications by repair enzymes is exploited for the analysis of DNA damage induced by visible light in the presence of methylene blue in Salmonella typhimurium. The relative frequencies of various endonuclease-sensitive sites and strand breaks are determined in the plasmid pAQ1 of the treated bacteria and are compared with those observed after exposure of isolated DNA to various conditions. This comparison of damage profiles indicates that the cellular DNA damage by illumination in the presence of methylene blue is caused predominantly by the direct action of singlet oxygen. Indirect mechanisms, e.g. involving a generation of superoxide and hydroxyl radicals or the activation of cellular nucleases, do not contribute very much. The damage is dominated by base modifications. These are subject to an efficient repair that is not mediated by uvrABC proteins and therefore most probably involves recognition by specific glycosylases. Revertant frequencies observed under these conditions in the strains TA1535, TA100, TA2638 and TA104 indicate a pronounced mutagenicity of the lesions induced. On the other hand, the DNA damage does not contribute significantly to the cytotoxicity caused by the treatment as an excision repair deficiency (uvrB) has no influence on cell killing.
Carcinogenesis 1989 Nov
PMID:Singlet oxygen as an ultimately reactive species in Salmonella typhimurium DNA damage induced by methylene blue/visible light. 268 Jan 44


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>