ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1978.tb07687.x

出版商:Blackwell Publishing Ltd    

年代:1978

数据来源: WILEY

摘要:

Abstract—In bacteria, three processes of DNA repair are known: photoreactivation, excision repair, and postreplication repair.Photoreactivation, the enzymatic splitting of cyclobutyl pyrimidine dimersin situ, is mediated by exposure of the enzyme‐dimer complex to near‐UV and visible light. This repair process appears to be error free. Theexcision repairof UV‐induced DNA base damage has been divided into two major pathways on the basis of both physiological requirements and genetic control. The major pathway requires a functionalpol Agene, does not require complete growth medium. and appears to be largely error‐free and to produce short patches during repair. The second pathway requires complete growth medium and functionalrecA, recB, recC, lexA, uvrD, andpolCgenes, and appears to be mutagenic and to produce long patches during repair. There exists a second type of excision repair in which the modified base is removed by anN‐glycosidase, and the chain is then nicked by an apurinic (apyrimidinic) acid endonuclease. Subsequent events are presumed to be similar to the above excision repair process. Thepostreplication repairsystem has been divided into at least four separate pathways. Three of these are dependent upon functionalrecB, lexA, anduvrDgenes, respectively, and appear to be error free. A fourth pathway depends upon the above gene products, but is blocked by postirradiation treatment with chloramphenicol, and may be the UV‐inducible, errorprone, mutagenic pathway of repair (“SOS repair”). A possible fifth pathway depends upon a functionalrecFgene, and is independent of therecB+‐dependent pathway.Mutagenesisappears to be the result of error‐prone DNA repair, and there is growing evidence that carcinogenesis is also the result of e

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1978.tb07688.x

出版商:Blackwell Publishing Ltd    

年代:1978

数据来源: WILEY

摘要:

Abstract—Mutations may result from imperfect DNA replication, unrepaired DNA damage, and errorprone DNA repair. DNA damage may induce any or all of these effects. Numerous physical and chemical agents damage DNA, and the repair of such damage may be either incomplete, error‐free, or error‐prone. It is assumed that correctly repaired DNA damage has no deleterious biological consequence. Unrepaired or misrepaired DNA damage has been related to such physiological changes as cell death, division suppression, gene repression and derepression, altered transcription, elevated cAMP levels, predisposition of the cell to viral transformation, decreased cellular respiration, and mutation. Defective DNA repair has been linked in man to cancer, birth defects, arteriosclerosis, high blood pressure, aging, and neurological dysfunction. Various clinical syndromes including xeroderma pigmentosum (XP), ataxia telangiectasia (AT), Fanconi's anemia (FA), progeria, actinic keratosis (AK), and possibly Cockayne syndrome (CS) have been described as being defective in at least one of the various forms of DNA repair.There are at least four general types of enzymatic repair systems in mammalian cells (excision, strand break, postreplication, and photoreactivation). Each of these, except the latter, is composed of multiple pathways. The two most intensely studied of these repair systems are excision and postreplication repair.Excision repair presumably involves the error‐free removal of damaged DNA by a complex of enzymes. The damaged segment is removed and replaced with newly synthesized DNA using the opposite strand as the template. A measure of excision repair may be made by assaying: (1) removal of known products; (2) production of single‐strand breaks following treatment of cellular DNA with damage‐specific endonuclease preparations; or (3) measurement of repair synthesis. Since (XP) individuals who are defective in the excision of ultraviolet (UV) light induced lesions are also defective in the repair of certain forms of chemically‐induced DNA damage, and since the size of repaired regions for both acetoxy‐acetylaminofluorene (AAAF) and UV‐induced DNA damage were believed to be similar, it was assumed that similar mechanisms for the repair of both physically and chemically‐induced DNA damage existed. Recent evidence, however, suggests that significant differences may exist in the repair of DNA damage induced by agents producing similar patch sizes. Excision repair capacity also appears to vary as a function of species, organ, state of differentiation, and pattern of chromatin association with DNA. Although there appear to be several enzymes specific for the recognition of specific forms of DNA damage, once recognition (nicking) has occurred, the subsequent sequence of events for most types of excision repair are presumed to be similar.Postreplication repair, which presumably may be either error‐free or error‐prone, is a process in which DNA, newly‐synthesized from a defective or damaged template, is repaired. Postreplication repair is usually studied by observing that the newly‐synthesized DNA from damaged templates contains gaps that disappear with time. In human cells, the number of gaps approximately equals the number of lesions. This system is important in actively dividing cells and cells that have been induced to divide. XP “variant” cells, which are normal for excision repair, have been shown to be defective in postreplication repair. However, in cell cultures that have been treated with either physical or chemical mutagens and DNA replication blocked following such treatment, the mutation frequency per dose decreases as a function of the duration of mitotic blockage. These data thus suggest a role in mammalian cell mutagenesis for an error‐prone postreplication repair system as well as misinsertion during DNA replication.This paper will discuss various mammalian cell DNA repair processes, the role of specific forms of DNA damage in cellular mutagenesis, and mammalian repair defective mutant cell lines. An attempt will be made to correlate these items plus what is known in bacterial mutagenesis to potential mechanisms f

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1978.tb07689.x

出版商:Blackwell Publishing Ltd    

年代:1978

数据来源: WILEY

摘要:

Abstract—Since the neoplastic condition is a phenotypic expression of the genome of the tumor cells, it is reasonable to assume that the neoplastic state can be the result of the alteration of gene activity by either mutagenesis or gene modulation. The review of the literature seems to support the hypothesis that both mutations and epigenetic processes are components to carcinogenesis. Consistent with the mutation theory of cancer are: (1) the clonal nature of tumors; (2) the mutagenicity of most (but not all) carcinogens; (3) correlation of high mutation frequencies in cells of cancer‐prone human fibro‐ blasts lacking DNA repair enzymes; (4) correlation ofin vitroDNA damage,in vitromutation and transformation frequencies within vivotumorigenesis; (5) age‐related incidences of various hereditary tumors; and (6) the correlation between photoreactivation of DNA damage and the biological amelioration of UV‐induced neoplasms. Supporting the epigenetic theory of carcinogenesis is the reversion of certain types of neoplastic cells to a state allowing normal development. These latter studies demonstrate the totipotency of the genes in some types of malignant cells.An integrative theory of carcinogenesis is presented that synthesizes the mutation and epigenetic theories with Comings' general theory of carcinogenesis and the 2‐stage theory of carcinogenesis. Data are presented that test the predictions of the 2‐stage theory of carcinogenesis, and that support the hypothesis that mutagenesis plays a major role in carcinogenesis (initiation phase) and that gene modulation of repressed mutations is responsible for tu

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1978.tb07690.x

出版商:Blackwell Publishing Ltd    

年代:1978

数据来源: WILEY

摘要:

Abstract—Primary photochemical processes in aqueous solution have been characterised for FMN. The influence of pH on these processes is attributed to protonation of the neutral triplet and not to the presence of a dimeric species as postulated earlier. Second order rate constants for reaction between the neutral triplet and some naturally occurring amino acids are reporte

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1978.tb07691.x

出版商:Blackwell Publishing Ltd    

年代:1978

数据来源: WILEY

摘要:

Abstract—Laser flash photolysis at 265 nm has been employed for measuring the initial hydrated electron (e‐aq) andp‐alanylphenoxyl radical (Tyr) in aqueous Tyr, small Tyr peptides and R Nase A. The results indicate that monophotonic photolysis not involving the fluorescent or triplet states is the principal initial process. Equivalent yields of e and Tyr were found in all cases except Tyr, where the Tyr yield was 60% higher than e‐aqattributed to splitting of the phenolic bond. Computer analysis of e‐aqand Tyr decays for Tyr indicates the importance of electron‐radical recombination in competition with electron scavenging and bimolecular radical‐radical reactions. Evidence for intramolecular electron migration has been obtained in cys

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1978.tb07692.x

出版商:Blackwell Publishing Ltd    

年代:1978

数据来源: WILEY

摘要:

Abstract—The 3‐tyrosinyl free radicals (3‐Tyr) and iodine atom are formed by flash photolysis of 3‐iodotyrosine (3‐Tyr‐I) in aqueous solutions at pH 5. The presence of iodine atoms in the medium is characterized by the absorption spectrum and the decay kinetics of I formed when KI is added to the system. In the absence of radical scavengers, the 3‐Tyr adds to or reacts with the parent molecule to produce a transient species, probably a radical dimer, which has an absorption maximum at 405 nm. The decay of this transient follows second order kinetics whose rate constant increases with decreasing 3‐iodotyrosine concentration. Measurements of the dependence of the transient yield on the concentration of added ethanol indicate that the 3‐Tyr radical reacts with ethanol by hydrogen abstraction. The rate constants of reaction of the 3‐Tyr radical with 3‐iodotyrosine and ethanol are

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1978.tb07693.x

出版商:Blackwell Publishing Ltd    

年代:1978

数据来源: WILEY

摘要:

Abstract—The induction by near UV light of growth delay inBacillus subtiliswas studied utilizing a menaquinone‐deficient (men–) strain. Menaquinone appears to be a target molecule in this bacterial species, in view of the following: (i) themen–strain requires menaquinone precursors to terminate growth delay; (ii) the menaquinone synthesis inhibitor diphenylamine prolongs growth delay; (iii) themen–strain must be phenotypically Men* at the time of near UV irradiation to induce growth delay. These findings suggest that growth delay inB. subtilismay be associated with a prerequisite removal of photochemically altered menaquinone from the cytoplasmic membrane, rather than simply the time required for resynthesis of menaquinone. Alternatively, the altered menaquinone may inhibit some critical reaction(s) of intermediary metabolism or macromolecular

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1978.tb07694.x

出版商:Blackwell Publishing Ltd    

年代:1978

数据来源: WILEY

摘要:

Abstract—The photodynamic action of protoporphyrin on red cell ghosts is reflected by extensive cross‐linking of membrane proteins to very high molecular weight protein aggregates. This process was studied with sepharose gel chromatography and sodium dodecyl sulphate polyacrylamide gel electrophoresis.Most sensitive to this photodynamic effect are spectrin and band 2. 1, 2. 2, 2.3 and 4.1. polypeptides, which are cross‐linked after very brief illumination periods, with a concomitant loss of spectrin‐associated ATPase activity. Band 6 protein, representing the monomeric form of glyceraldehyde‐3‐phosphate dehydrogenase, is also very sensitive to protoporphyrin‐induced cross‐linking. The enzymatic activity decreased even faster than the amount of band 6 polypeptides, suggesting that modification(s) of the enzyme other than cross‐linking, possibly by rapid photooxidation of a thiol group, may be responsible for inactivation.Extracted and purified spectrin was cross‐linked with about the same velocity as membrane‐bound spectrin, reinforcing our previously drawn conclusion that membrane lipids are not involved in the cross‐linking reaction. Eluted band 6 polypeptides on the other hand exhibited a relatively fast photo‐oxidative modification but a much slower cross‐linking to dimers and tetramers. This suggests that the membrane structure, e.g. the spectrin matrix may play an essential role in the incorporation of membrane‐bound band 6 polypeptides in the high molecula

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1978.tb07695.x

出版商:Blackwell Publishing Ltd    

年代:1978

数据来源: WILEY

摘要:

Abstract—The fluorescence spectra of various reduced bacteriorhodopsin chromophore species indicate energy transfer from aromatic amino acid side chains of the protein to the retinyl moiety. Binding studies with retinol reveal that energy transfer occurs only when the retinyl moiety is bound in the chromophoric site of the protein. Retroretinol is a fluorescent probe for the binding sit

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1978.tb07696.x

出版商:Blackwell Publishing Ltd    

年代:1978

数据来源: WILEY