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STRUCTURAL BIOLOGY OF POLY(ADP-ribose) POLYMERASE ENZYMES

They demonstrated
Abeta(25-35)-induced apoptosis in PC12 cells by: (1) a dose-dependent loss of cell viability; (2) a time- and
dose-dependent increase in the apoptotic cells; (3) an induction of DNA fragmentation; and (4) an increase in
caspase-3 activity and cleavage of poly (ADP-ribose) polymerase (PARP).

POLY (ADP-RIBOSE) POLYMERASE 1 IN DNA DAMAGE RECOGNITION

AB - Poly(ADP-ribose) polymerase (PARP) enzymes catalyze the conversion of NAD+ to polymers of poly(ADP-ribose) (PAR). Although its role in the DNA-damage response has long been recognized, recent work indicates that PAR itself acts at the mitochondria to directly induce cell death through stimulation of apoptosis-inducing factor (AIF) release. This review discusses PAR synthesis and degradation, and the role of PAR misregulation in various disease states. Attention is given to opportunities for therapeutic intervention with small molecules that are involved in PAR signaling, with specific focus on poly(ADP-ribose) glycohydrolase (PARG) and AIF.

Inhibition of Poly(ADP-Ribose) Polymerase in Tumors …

N2 - Poly(ADP-ribose) polymerase (PARP) enzymes catalyze the conversion of NAD+ to polymers of poly(ADP-ribose) (PAR). Although its role in the DNA-damage response has long been recognized, recent work indicates that PAR itself acts at the mitochondria to directly induce cell death through stimulation of apoptosis-inducing factor (AIF) release. This review discusses PAR synthesis and degradation, and the role of PAR misregulation in various disease states. Attention is given to opportunities for therapeutic intervention with small molecules that are involved in PAR signaling, with specific focus on poly(ADP-ribose) glycohydrolase (PARG) and AIF.

The remarkable stability of the human genome is lost in cancer cells due to the failure of efficient and accurate repair in the context of oncogene-induced replication stress and elevated transcription. DNA replication is furthermore emerging as a surprisingly fragile and complex process requiring fork protection and restart, template-switching, R-loop resolution, gap-filling, and repair. Unresolved replication and repair intermediates signal apoptosis. The synthetic lethality and essentiality resulting from replication-repair stresses thus suggest repair inhibitors as tools to control pathway selection and damage outcomes and to design advanced therapeutics.

Poly(ADP-ribose): From chemical synthesis to drug …

fragments of poly(ADP-ribose) ..

Poly(ADP-ribose) polymerase (PARP) enzymes catalyze the conversion of NAD+ to polymers of poly(ADP-ribose) (PAR). Although its role in the DNA-damage response has long been recognized, recent work indicates that PAR itself acts at the mitochondria to directly induce cell death through stimulation of apoptosis-inducing factor (AIF) release. This review discusses PAR synthesis and degradation, and the role of PAR misregulation in various disease states. Attention is given to opportunities for therapeutic intervention with small molecules that are involved in PAR signaling, with specific focus on poly(ADP-ribose) glycohydrolase (PARG) and AIF.

They found a (1) significant
increase in ROS formation preceded apoptotic events after exposuring PC12 cells to Abeta(25-35)and (2)
PYC not only suppressed the generation of ROS but also attenuated caspase-3 activation, DNA
fragmentation, PARP cleavage, and eventually protected against Abeta-induced apoptosis.

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Stimulation of poly(ADP-ribose) synthesis by free …

Meindert Lamers (Leiden University Medical Center)
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Susan Lees-Miller (Arnie Charbonneau Cancer Institute)
'NON-REPAIR FUNCTIONS OF DNA-PKcs'

Karolin Luger (University of Colorado at Boulder)
'POLY (ADP-RIBOSE) POLYMERASE 1 IN DNA DAMAGE RECOGNITION'

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Katharina Schlacher (MD Anderson Cancer Center)
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David Schriemer (University of Calgary)
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Titia Sixma (NKI)
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Maria Spies (University of Iowa)
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Terence Strick (Institut Jacques Monod)
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Madalena Tarsounas (The CR-UK/MRC Oxford Institute for Radiation Oncology)
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