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1.
Role of poly(ADP-ribose) formation in DNA repair.   总被引:39,自引:0,他引:39  
M S Satoh  T Lindahl 《Nature》1992,356(6367):356-358
The abundant nuclear enzyme poly(ADP-ribose) polymerase catalyses the synthesis of poly(ADP-ribose) from nicotinamide adenine dinucleotide (NAD+). This protein has an N-terminal DNA-binding domain containing two zinc-fingers, which is linked to the C-terminal NAD(+)-binding domain by a short region containing several glutamic acid residues that are sites of auto-poly(ADP-ribosyl)ation. The intracellular production of poly(ADP-ribose) is induced by agents that generate strand interruptions in DNA. The branched homopolymer chains may attain a size of 200-300 residues but are rapidly degraded after synthesis. The function of poly(ADP-ribose) synthesis is not clear, although it seems to be required for DNA repair. Here we describe a human cell-free system that enables the role of poly(ADP-ribose) synthesis in DNA repair to be characterized. The results indicate that unmodified polymerase molecules bind tightly to DNA strand breaks; auto-poly(ADP-ribosyl)ation of the protein then effects its release and allows access to lesions for DNA repair enzymes.  相似文献   

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Regulation of DNA ligase activity by poly(ADP-ribose)   总被引:32,自引:0,他引:32  
D Creissen  S Shall 《Nature》1982,296(5854):271-272
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Requirement for the replication protein SSB in human DNA excision repair   总被引:40,自引:0,他引:40  
D Coverley  M K Kenny  M Munn  W D Rupp  D P Lane  R D Wood 《Nature》1991,349(6309):538-541
Replication and repair are essential processes that maintain the continuity of the genetic material. Dissection of simian virus 40 (SV40) DNA replication has resulted in the identification of many eukaryotic replication proteins, but the biochemistry of the multienzyme process of DNA excision repair is less well defined. One protein that is absolutely required for semiconservative replication of SV40 DNA in vitro is human single-stranded DNA-binding protein (SSB, also called RF-A and RP-A). SSB consists of three polypeptides of relative molecular mass 70,000, 34,000 and 13,000, and acts with T antigen and topoisomerases to unwind DNA, allowing the access of other replication proteins. Human SSB can also stimulate the activity of polymerases alpha and delta, suggesting a further role in elongation during DNA replication. We have now found a role for human SSB in DNA excision repair using a cell-free system that can carry out nucleotide excision repair in vitro. Monoclonal antibodies against human SSB caused extensive inhibition of DNA repair in plasmid molecules damaged by ultraviolet light or acetylaminofluorene. Addition of purified SSB reversed this inhibition and further stimulated repair synthesis by increasing the number of repair events. These results show that a mammalian DNA replication protein is also essential for repair.  相似文献   

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Nucleosome structure controls rates of excision repair in DNA of human cells   总被引:10,自引:0,他引:10  
J E Cleaver 《Nature》1977,270(5636):451-453
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Min JH  Pavletich NP 《Nature》2007,449(7162):570-575
Mutations in the nucleotide excision repair (NER) pathway can cause the xeroderma pigmentosum skin cancer predisposition syndrome. NER lesions are limited to one DNA strand, but otherwise they are chemically and structurally diverse, being caused by a wide variety of genotoxic chemicals and ultraviolet radiation. The xeroderma pigmentosum C (XPC) protein has a central role in initiating global-genome NER by recognizing the lesion and recruiting downstream factors. Here we present the crystal structure of the yeast XPC orthologue Rad4 bound to DNA containing a cyclobutane pyrimidine dimer (CPD) lesion. The structure shows that Rad4 inserts a beta-hairpin through the DNA duplex, causing the two damaged base pairs to flip out of the double helix. The expelled nucleotides of the undamaged strand are recognized by Rad4, whereas the two CPD-linked nucleotides become disordered. These findings indicate that the lesions recognized by Rad4/XPC thermodynamically destabilize the Watson-Crick double helix in a manner that facilitates the flipping-out of two base pairs.  相似文献   

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Using agarose gel electrophoresis and T4-endodeoxyribonuclease-V, which is a kind of restriction endonuclease of cyclobutyl pyrimidine dimer (CPD), the impacts of He-Ne laser (5 mW · mm−2) irradiation on DNA excision repair capacity in damaged wheat cells induced by enhanced ultraviolet-B (10.08 kJ ·m−2 ·d−1) radiation were studied. The results indicated that the content of endonuclease sensitive sites (ESS) was reduced by He-Ne laser irradiation, which formed in cells irradiated by enhanced ultraviolet-B. With the irradiation of He-Ne laser, the excision of CPDs and the reduction of single strand breaks (SSB) contents which were the endonuclease sensitive sites (ESS) digested by T4-endodeoxyribonuclease-V had been stimulated in the wheat cells.  相似文献   

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设n是正整数,运用初等方法证明了丢番图方程(16n)x+(63n)y=(65n)z仅有整数解(x,y,z)=(2,2,2),从而得到了Jesmanowicz猜想在该情形下成立.  相似文献   

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当F是无限域,K是F的子域,且[ F:K] < n(n - 1) 时,本文给出了GL(n ,k)在GL(n ,F) 中的全部扩群,从而得出GL( n,F) 的一类极大子群  相似文献   

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The Busemann function plays a very important role in studying topology and geometry of a complete Riemannian manifold. In this paper, the Busemann functions on the real classical domain of the first type and the Cartan domain of the fourth type in the explicit formulas are obtained.  相似文献   

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Xeroderma pigmentosum (XP) is an autosomal recessive disease, characterized by a high incidence of sunlight-induced skin cancer. Cells from people with this condition are hypersensitive to ultraviolet because of a defect in DNA repair. There are nine genetic complementation groups of XP, groups A-H and a variant. We have cloned the mouse DNA repair gene that complements the defect of group A, the XPAC gene. Here we report molecular cloning of human and mouse XPAC complementary DNAs. Expression of XPAC cDNA confers ultraviolet-resistance on several group A cell lines, but not on lines of other XP groups. Almost all group A lines tested showed abnormality or absence of XPAC messenger RNAs. These results indicate that a defective XPAC gene causes group A XP. The human and mouse XPAC genes are located on chromosome 9q34.1 and chromosome 4C2, respectively. Human XPAC cDNA encodes a protein of 273 amino acids with a zinc-finger motif.  相似文献   

17.
A new method has been developed to assay poly(ADP-ribose) polymerase (PARP) activity in plant tissues through determining the content of nicotinamide (NIC) produced by enzymatic reaction by linear sweeping polarographic method. The detection limit of NIC was 0.03μmol/L, the calibration graph was linear up to 5 Mmol/L ( r = 0.999). The recoveries were approximately in the range of 92% to 98% and the relative standard deviations were less than 6.6% . Moreover, NAD+ and other interference existing in the mixture after enzymatic reaction had been removed by simple pretreatment, thus PARP assays were not interfered. A rapid, simple, sensitive and reliable nonisotopic method is reported to assay PARP activity in plant tissues . The results show that the KmNAD+ value of PARP in maize ( Zea mays L.) seedlings is 59 and the optimum pH for PARP activity is 8.5. Moreover, physiological conditions affect PARP activity in plant tissues, which has not been reported previously. When tobacco ( Nico-tiana tobacum) suspension cells were stressed by NaCI at low concentrations (100, 200 mmol/ L), the PARP activity increased significantly; when the cells were stressed at high concentrations (400, 1 000 mmol/L), it decreased to or even below the control level. PARP activity in etiolated maize seedlings was higher than that in light-grown seedlings.  相似文献   

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设φ(n)表示n的欧拉函数,σ(n)表示n的所有正因子和,ω(n)表示n的不同素因子的个数.对于整除关系φ(n)|σ(n),其中n是正整数,当n为素数时只对n=2,3成立.讨论了当n至多有3个不同的素因子时,n为哪些合数时才能使该整除式成立,其中解2α(2α 2-1)(其中2α 2-1为素数,α∈N)与偶完全数2n-1(2n-1)(其中2n-1为素数且n∈N)类似.  相似文献   

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The Busemann function plays a very important role in studying topology and geometry of a complete Riemannian manifold. In this paper, the Busemann functions on the real classical domain of the first type and the Cartan domain of the fourth type in the explicit formulas are obtained.  相似文献   

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