PolyADP-Ribose

The existence of Poly-ADP-ribose (10.94) has been confirmed [63]. It has a highly branched structure. Moreover is believed to have important bio functions and may be linked to DNA damage and apoptosis [64]. The highly branched structure is subject to cleavage at different points depending upon which enzymes are present. 

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PARP polyADP-ribose polymerase PtdOH phosphatidic acid... 

Tutt A, Robson M, Garber JE et al (2010) Oral polyADP-ribose polymerase inhibitor olaparib in patients with BRCAl or BRCA2 mutations and advanced breast cancer a proof-of- concept trial. Lancet 376 235-244... 

Drew Y, Mulligan EA, Vong WT et al (2011) Therapeutic potential of polyADP-ribose polymerase inhibitor AGO 14699 in human cancers with mutated or methylated BRCAI or BRCA2. J Nat Cancer Ins 103 334-346... 

Wiltshire TD, Lovejoy CA, WangT et al (2010) Sensitivity to polyADP-ribose polymerase PARP inhibition identifies ubiquitin-specific peptidase 11 USPll as a regulator of DNA double-strand break repair. J Biol Chem 285 14565-14571... 

B, Aboukameel A, Pettit GR, Al-Katib AM. Combretastatin-A4 prodrug induces mitotic catastrophe in chronic lymphocytic leukemia cell line independent of caspase activation 87. and polyADP-ribose polymerase cleavage. Clin. Cancer Res. 2002 8 2735-2741. 

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]. 

Kannan P, Yu Y, Wankhade S et al. PolyADP-ribose polymerase is a coactivator for AP-2-mediated transcriptional activation. Nucleic Acids Res 1999 27(3) 866-874. 

Doly J, Petek F (1966) Etude de la structure d un compose polyADP-ribose synthetise par des extraits nucleaires de foie du poulet. C R Acad Sd 263 1341-1344... 

Mandel P, Bergerat JP, Dufour P, Herbrecht R (1983) Inhibition de la polyADP-ribose synthetase, voie nouvelle dans la recherche d une reduction de la proliferation cellulaire. Bull Acad Nat Med Paris 167 327-332... 

Only the initial phase of mono(ADP-ribosyl)ation by polyADP(ribose) transferase at very low concentrations of NAD+ approximates Michaelis-Menten kinetics (14). At saturating concentrations of NAD+ the rate of polymer formation, which follows a Poisson distribution (14), becomes important. Therefore the relationship between overall velocity and NAD+ concentration cannot be described by a simple rate equation. Because of these complications we compare the catalytic efficiencies of octamers by correlating polyADP(ribose) transferase activity with the concentration of octamers varying over a very large range. Also binding constants (ko) of the octamers and sDNA to polyADP(ribose) were calculated (Table 1). 

Qian, J. J., Duncan, B., Adzick, N. 8., and Bhatnagar, R. 8., 1993, Regulation of prolyl hydroxylase by ascorbic acid is mediated by polyADP-ribose synthesis. Cell. Mol. Biol. Res. 39 525-533. 

In addition to its coenzyme role, NAD is the source of ADP-ribose for the ADP-ribosylation of proteins and polyADP-ribosylation of nucleoproteins involved in the DNA repair mechanism. 

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