Biomaterial Database

DNA strand break-mediated partitioning of poly(ADP-ribose) polymerase function. 1994

P L Panzeter, and F R Althaus

Institute of Pharmacology and Toxicology, University of Zürich-Tierspital, Switzerland.

The nuclear enzyme poly(ADP-ribose) polymerase participates in DNA excision repair. Following binding to DNA strand breaks through its amino-terminal Zn(2+)-finger domain, the enzyme is activated to form polymerase-associated ADP-ribose polymers of various sizes. Focusing on this "automodification" reaction, we observed that optimal enzyme activity and maximal polymer formation were attained only at a strict stoichiometry of two polymerase molecules per DNA fragment. Using various linearized DNAs and nicked circular DNA, we show that this stoichiometric dependence is dictated by the number of enzyme activating sites, i.e., DNA strand breaks. Deviations from the optimal ratio inevitably resulted in decreased polymer formation, ruling out a strict automodification mechanism of poly(ADP-ribosyl)ation. Our results suggest that the mechanism of poly(ADP-ribose) formation on polymerase molecules entails DNA strand break-mediated partitioning of the polymerase into two functional populations: one bound to the DNA breaks and catalytically active, the other, catalytically inactive, functioning as polymer acceptors.

UI	MeSH Term	Description	Entries
D011065	Poly(ADP-ribose) Polymerases	Enzymes that catalyze the transfer of multiple ADP-RIBOSE groups from nicotinamide-adenine dinucleotide (NAD) onto protein targets, thus building up a linear or branched homopolymer of repeating ADP-ribose units i.e., POLY ADENOSINE DIPHOSPHATE RIBOSE.	ADP-Ribosyltransferase (Polymerizing),Poly ADP Ribose Polymerase,Poly(ADP-Ribose) Synthase,Poly(ADP-ribose) Polymerase,PARP Polymerase,Poly ADP Ribose Transferase,Poly ADP-Ribose Synthase,Poly(ADP-Ribose) Transferase,Poly(ADPR) Polymerase,Poly(ADPribose) Polymerase,Poly ADP Ribose Synthase,Polymerase, PARP,Synthase, Poly ADP-Ribose
D011485	Protein Binding	The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.	Plasma Protein Binding Capacity,Binding, Protein
D004249	DNA Damage	Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.	DNA Injury,DNA Lesion,DNA Lesions,Genotoxic Stress,Stress, Genotoxic,Injury, DNA,DNA Injuries
D004279	DNA, Viral	Deoxyribonucleic acid that makes up the genetic material of viruses.	Viral DNA
D004789	Enzyme Activation	Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.	Activation, Enzyme,Activations, Enzyme,Enzyme Activations
D013539	Simian virus 40	A species of POLYOMAVIRUS originally isolated from Rhesus monkey kidney tissue. It produces malignancy in human and newborn hamster kidney cell cultures.	SV40 Virus,Vacuolating Agent,Polyomavirus macacae,SV 40 Virus,SV 40 Viruses,SV40 Viruses,Vacuolating Agents