Poly polymerase repair

The enzyme catalyzing the addition of ADP-ribose units onto the histones and itself is poly(ADP-ribose) polymerase or synthetase. Poly(ADP-ribose) polymerase is a nuclear, DNA-dependent enzyme that is stimulated by DNA breaks [302]. This property of the enzyme would target its action to sites that have DNA strand breaks (regions of the genome involved in replication, repair, recombination). The enzyme is associated with chromatin areas and perichromatin regions in interphase Chinese hamster ovary cells [312]. Degradation of the ADP-ribose polymer is catalyzed by the nuclear enzyme poly(ADP-ribose) glycohydrolase and ADP-ribosyl protein lyase. 

Realini and Althaus [313] have put forth the hypothesis that poly(ADP-ribosylation) may have a function in histone shuttling. They propose that poly(ADP-ribose) polymerase directed to sites of DNA strand breaks would auto-modify itself generating multiple ADP-ribose polymers. The polymers would lead to the dissociation of the histones from DNA onto the polymers. The DNA would now be free for processing (e.g., by enzymes involved in excision repair). The action of poly(ADP-ribose) glycohydrolase would degrade the... 

PARP binds to DNA surrounding single- or double-strand breaks and attaches polymers of ADP-ribose to itself and other proteins. This increases the negative charge in this area, thus facilitating DNA repair. Payne et al. reported increased poly(ADP-ribose) polymerase (PARP) activity in Jurkat cells treated with sodium deoxycholate. Activation of PARP in colonic cells was similarly reported by Glinghammer et al " following treatment with this bile acid. 

Tracco, C., Oliver, F.J., de Murcia, G. and Menissier-de Murcia, J. (1998) DNA repair defect in poly(ADP-ribose) polymerase-deficient cell lines. Nucleic Acids Res., 26, 2644-2649. 

Vodenicharov, M.D., Sallmann, F.R., Satoh, M.S. and Poirier, G.G. (2000) Base excision repair is efficient in cells lacking poly(ADP-ribose) polymerase 1. Nucleic. Acids. Res., 28, 3887-3896. 

Yung, T.M.C. and Satoh, M.S. (2001). Functional competition between poly(ADP-ribose) polymerase and Its 24-kDa apoptotic fragment in DNA repair and transcription. J. Biol. Chem., 276, 11279-11286. 

The best-established function of poly(ADP-ribose) polymerase is in repair of damaged DNA it is activated by DNA strand breaks, and acts to clear histones and other nucleoproteins away from the DNA to permit access of the DNA repair enzymes. Both in vitro and in experimental animals, niacin deficiency leads to increased genomic instability, as the ability to repair damaged DNA is impaired, and may increase tumor risk. There is little information about genomic instability and cancer risk in human niacin deficiency (ffageman and Stiemm, 200f). 

A variety of other nuclear proteins are also targets for poly(ADP-ribo-sylation), including histones, topo-isomerases, DNAligases, and DNA-depen-dent RNA polymerase, suggesting that in addition to its role in DNA repair, polyfADP-ribose) polymerase may be important in DNA replication and transcription. In DNA replication, it controls the progression of the replication fork, and in preadipocytes, there is a considerable increase in activity in response to the induction of differentiation (Simbulan-Rosenthal et al., 1996). 

Poly (ADP-ribose) polymerase-1 (PARP-1) facilitates the repair of DNA strand breaks (Calabrese et al, 2004). Inhibiting PARP-1 increases the cytotoxicity of DNA-damaging chemotherapy and radiation therapy in vitro. But classical PARP-1 inhibitors have limited clinical utility. AG14361 is, to our knowledge, the first high-potency... 

Bhat, K.R., Benton, B.J., Rosenthal, D.S., Smulson, M.E., Ray, R. (2000). Role of poly(ADP-rihose) polymerase (PARP) in DNA repair in sulfur mustard-exposed normal human epidermal keratinoc des (NHEK). J. Appl. Toxicol. 20 S13-17. 

Schreiber V, et al. Poly(ADP-ribose) polymerase-2 (PARP-2) is required for efficient base excision DNA repair in association... 

Griffin RJ, et al. Resistance-modifying agents. 5. Synthesis and biological properties of quinazolinone inhibitors of the DNA 156. repair enzyme poly(ADP-ribose) polymerase (PARP). J. Med. 

ADP-ribosylation. In the case of some proteins, multiple ADP-ribose units are transferred to the protein, forming a poly(ADP-ribose) group. The activity of poly (ADP-ribose) polymerase is increased during cell growth, cell differentiation, and recovery from damage to the DNA. The enz)une is involved in controlling the repair of DNA (Satoh et al., 1993). 

Inactivation of DNA repair enzymes can also turn on apoptosis. A fascinating apoptotic process can result from stress or toxicity that culminates in genomic damage in the cell nucleus, triggered by a nuclear enzyme poly (ADP-ribose) polymerase... 

PNK phosphorylates the 5 -OH ends. The specialized BER polymerase and the ligase can then proceed. Anyhow, an early step in the repair of SSB appears to be the rapid binding by poly(ADP-ribose) polymerase-1 (PARP1), a nick sensor that is activated at SSB. PARP1 synthesizes negatively charged polyADP-ribose that may serve as scaffold for the binding of the repair proteins involved later in the process [8]. 

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