Journal ArticleDOI
Poly(ADP-ribose): novel functions for an old molecule.
TLDR
The addition to proteins of the negatively charged polymer of ADP-ribose (PAR), which is synthesized by PAR polymerases (PARPs) from NAD+, is a unique post-translational modification that regulates not only cell survival and cell-death programmes, but also an increasing number of other biological functions with which novel members of the PARP family have been associated.Abstract:
The addition to proteins of the negatively charged polymer of ADP-ribose (PAR), which is synthesized by PAR polymerases (PARPs) from NAD(+), is a unique post-translational modification. It regulates not only cell survival and cell-death programmes, but also an increasing number of other biological functions with which novel members of the PARP family have been associated. These functions include transcriptional regulation, telomere cohesion and mitotic spindle formation during cell division, intracellular trafficking and energy metabolism.read more
Citations
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Journal ArticleDOI
The DNA Damage Response: Making It Safe to Play with Knives
TL;DR: This review will focus on how the DDR controls DNA repair and the phenotypic consequences of defects in these critical regulatory functions in mammals.
Journal ArticleDOI
Sirtuins as regulators of metabolism and healthspan
TL;DR: The mammalian sirtuin protein family (comprising SIRT1–SIRT7) has received much attention for its regulatory role, mainly in metabolism and ageing, thereby acting as crucial regulators of the network that controls energy homeostasis and as such determines healthspan.
Journal ArticleDOI
Trapping of PARP1 and PARP2 by Clinical PARP Inhibitors
Junko Murai,Shar Yin N. Huang,Benu Brata Das,Amelie Renaud,Yiping Zhang,James H. Doroshow,Jiuping Ji,Shunichi Takeda,Yves Pommier +8 more
TL;DR: This study shows that PARP inhibitors trap the PARP1 and PARP2 enzymes at damaged DNA, providing a new mechanistic foundation for the rational application ofPARP inhibitors in cancer therapy.
Journal ArticleDOI
NAD+/NADH and NADP+/NADPH in Cellular Functions and Cell Death: Regulation and Biological Consequences
TL;DR: Future investigation into the metabolism and biological functions of NAD and NADP may expose fundamental properties of life, and suggest new strategies for treating diseases and slowing the aging process.
Journal ArticleDOI
New insights into the molecular and cellular functions of poly(ADP-ribose) and PARPs.
Bryan A. Gibson,W. Lee Kraus +1 more
TL;DR: This work has shown that the activity of PARP family members, such as PARP1 and PARP2, is tied to cellular signalling pathways, and through poly(ADP-ribosyl)ation (PARylation) they ultimately promote changes in gene expression, RNA and protein abundance, and the location and activity of proteins that mediate signalling responses.
References
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Journal ArticleDOI
Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy
Hannah Farmer,Nuala McCabe,Christopher J. Lord,Andrew Tutt,Andrew Tutt,Damian A. Johnson,Tobias B. Richardson,Manuela Santarosa,Krystyna J. Dillon,Ian Hickson,Charlotte Knights,Niall M. B. Martin,Stephen P. Jackson,Graeme C. M. Smith,Alan Ashworth +14 more
TL;DR: BRCA1 or BRCA2 dysfunction unexpectedly and profoundly sensitizes cells to the inhibition of PARP enzymatic activity, resulting in chromosomal instability, cell cycle arrest and subsequent apoptosis, illustrating how different pathways cooperate to repair damage.
Journal ArticleDOI
Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase
Helen E. Bryant,Nilklas Schultz,Huw D. Thomas,Kayan M. Parker,Dan Flower,Elena Lopez,Suzanne Kyle,Mark Meuth,Nicola J. Curtin,Thomas Helleday,Thomas Helleday +10 more
TL;DR: It is proposed that, in the absence of PARP1, spontaneous single-strand breaks collapse replication forks and trigger homologous recombination for repair and exploited in order to kill BRCA2-deficient tumours by PARP inhibition alone.
Journal ArticleDOI
Mediation of poly(ADP-ribose) polymerase-1-dependent cell death by apoptosis-inducing factor.
Seong-Woon Yu,Hongmin Wang,Marc F. Poitras,Carmen Coombs,William J. Bowers,Howard J. Federoff,Guy G. Poirier,Ted M. Dawson,Valina L. Dawson +8 more
TL;DR: It is shown that PARP-1 activation is required for translocation of apoptosis-inducing factor (AIF) from the mitochondria to the nucleus and that AIF is necessary for PARp-1–dependent cell death.
Journal ArticleDOI
The PARP superfamily.
TL;DR: This review summarizes the present knowledge of this emerging superfamily of Poly(ADP‐ribose) polymerases, which might ultimately improve pharmacological strategies to enhance both antitumor efficacy and the treatment of a number of inflammatory and neurodegenerative disorders.
Journal ArticleDOI
Increased nuclear NAD biosynthesis and SIRT1 activation prevent axonal degeneration.
TL;DR: It is demonstrated that increased Nmnat activity is responsible for the axon-sparing activity of the Wlds protein and that SIRT1, a mammalian ortholog of Sir2, is the downstream effector of increased NMNat activity that leads to axonal protection.