Journal ArticleDOI
Single-strand break repair and genetic disease
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TLDR
The molecular mechanisms and organization of the DNA-repair pathways that remove single-strand breaks are reviewed and the connection between defects in these pathways and hereditary neurodegenerative disease are discussed.Abstract:
Hereditary defects in the repair of DNA damage are implicated in a variety of diseases, many of which are typified by neurological dysfunction and/or increased genetic instability and cancer. Of the different types of DNA damage that arise in cells, single-strand breaks (SSBs) are the most common, arising at a frequency of tens of thousands per cell per day from direct attack by intracellular metabolites and from spontaneous DNA decay. Here, the molecular mechanisms and organization of the DNA-repair pathways that remove SSBs are reviewed and the connection between defects in these pathways and hereditary neurodegenerative disease are discussed.read more
Citations
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The DNA-damage response in human biology and disease
Stephen P. Jackson,Jiri Bartek +1 more
TL;DR: The authors' improving understanding of DNA-damage responses is providing new avenues for disease management, and these responses are biologically significant because they prevent diverse human diseases.
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.
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Cell cycle, CDKs and cancer: a changing paradigm
TL;DR: Genetic evidence suggests that tumour cells may also require specific interphase CDKs for proliferation, and selective CDK inhibition may provide therapeutic benefit against certain human neoplasias.
Journal ArticleDOI
DNA Damage, Aging, and Cancer
TL;DR: Evidence that cancer and diseases of aging are two sides of the DNAdamage problem is presented, followed by an account of the derailment of genome guardian mechanisms in cancer and of how this cancerspecific phenomenon can be exploited for treatment.
Journal ArticleDOI
Dynamics of DNA damage response proteins at DNA breaks: a focus on protein modifications
TL;DR: How the development of various complementary methodologies has provided valuable insights into the spatiotemporal dynamics of DDR protein assembly/disassembly at sites of DNA strand breaks in eukaryotic cells is outlined.
References
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Journal ArticleDOI
Hydrogen peroxide-induced injury of cells and its prevention by inhibitors of poly(ADP-ribose) polymerase
Ingrid U. Schraufstatter,Paul A. Hyslop,D B Hinshaw,Roger G. Spragg,Larry A. Sklar,Charles G. Cochrane +5 more
TL;DR: In the current studies, inhibition of poly(ADP-ribose) polymerase by 3-aminobenzamide, nicotinamide, or theophylline in cells exposed to lethal concentrations of H2O2 prevented the sequence of events that eventually led to cell lysis--i.e., the decrease in NAD, followed by depletion of ATP, influx of extracellular Ca2+, actin polymerization and, finally, cell death.
Journal ArticleDOI
Chromatin Loosening by Poly(ADP)-Ribose Polymerase (PARP) at Drosophila Puff Loci
TL;DR: It is proposed that chromosomal PARP molecules become activated by developmental or environmental cues and strip nearby chromatin proteins off DNA to generate a puff.
Journal ArticleDOI
AP endonuclease-independent DNA base excision repair in human cells
Lee R Wiederhold,John B. Leppard,Padmini S. Kedar,Feridoun Karimi-Busheri,Aghdass Rasouli-Nia,Michael Weinfeld,Alan E. Tomkinson,Alan E. Tomkinson,Tadahide Izumi,Rajendra Prasad,Samuel H. Wilson,Sankar Mitra,Tapas K. Hazra +12 more
TL;DR: It is shown that in mammalian cells, removal of the 3' phosphate is dependent on polynucleotide kinase (PNK), and not APE, and that NEIL1/PNK could also repair the products of other DNA glycosylases, suggesting a broad role for this APE-independent BER pathway in mammals.
Journal ArticleDOI
The gene mutated in ataxia-ocular apraxia 1 encodes the new HIT/Zn-finger protein aprataxin
Maria-Ceu Moreira,Maria-Ceu Moreira,Clara Barbot,Nobutada Tachi,Naoki Kozuka,Eiji Uchida,Toby J. Gibson,P. Mendonça,Manuela Costa,José Barros,Takayuki Yanagisawa,Mitsunori Watanabe,Yoshio Ikeda,Masashi Aoki,Tetsuya Nagata,Paula Coutinho,Jorge Sequeiros,Michel Koenig +17 more
TL;DR: The results suggest that aprataxin is a nuclear protein with a role in DNA repair reminiscent of the function of the protein defective in ataxia-telangiectasia, but that would cause a phenotype restricted to neurological signs when mutant.
Journal ArticleDOI
Defective DNA single-strand break repair in spinocerebellar ataxia with axonal neuropathy-1
Sherif F. El-Khamisy,Gulam Mustafa Saifi,Michael Weinfeld,Fredrik Johansson,Thomas Helleday,Thomas Helleday,James R. Lupski,Keith W. Caldecott +7 more
TL;DR: It is reported that TDP1 is sequestered into multi-protein single-strand break repair (SSBR) complexes by direct interaction with DNA ligase IIIα and that these complexes are catalytically inactive in SCAN1 cells, and implicate this process in the maintenance of genetic integrity in post-mitotic neurons.