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Journal of Environmental Pathology, Toxicology and Oncology

ISSN for PRINT: 0731-8898

Institutional price:	$672.00
Issues per year:	4

Best Paper Award Selection - Editorial Board Site

2004, Volume23

88 pages

DOI: 10.1615/JEnvPathToxOncol.v23.i1

Issue price - $160.00

Poly (ADP-Ribose) Polymerase and DNA-Dependent Protein Kinase: Differential Activation In Vivo

Himanshi Narang
Radiation Biology and Health Sciences Division, Bhabha Atomic Research Center, Mumbai, India

Malini Krishna
Radioprotection and Decontamination Section, Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai-400085, India

Naresh C. Verma
Radiation Biology Division, Bhabha Atomic Research Centre, Mumbai, Pin. (400 085), India

ABSTRACT

DNA damage-activated homodimer of PARP-1 binds to single-strand breaks and catalyzes the synthesis and transfer of negatively charged ADP-ribose polymers to nuclear protein acceptors, including itself. It also undergoes site-specific proteolysis during apoptosis. On the other hand, DNA-PK is a heterotrimeric enzyme that specifically binds to double-strand breaks and phosphorylates its target proteins. Because both DNA breaks and apoptosis are known to occur following irradiation, whole-body irradiation was administered to find out the temporal pattern and dose—response of PARP expression and the activity pattern of DNA-PK. To assess the temporal response, male Wistar rats were subjected to a radiation dose of 3Gy and killed at various time intervals (1—24 hours). Both the PARP activity and expression were enhanced 4 hours after irradiation. Fragmented PARP was not observed until 24 hours after irradiation. The differential expression at DNA-PK various doses (0.1—5.0 Gy) was examined. The maximum expression of PARP was noted at 1 Gy, whereas the activation of DNA-PK was maximally observed at 3 Gy. We did not observe any increase in the expression of PARP until the dose of 3Gy was reached, which contradicted the findings in previous in vitro reports of PARP activation at high radiation doses. DNA-PK, however, showed a dose-dependent increase. Our results indicate that although both the PARP and the DNA-PK are nuclear enzymes with similar roles, the activation of these enzymes is dependent on the dose, and any extrapolation of data from in vitro observations can lead to misinterpretation.