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.
Journal ArticleDOI
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
Poly(ADP-ribose) Binds to Specific Domains in DNA Damage Checkpoint Proteins
TL;DR: The poly(ADP-ribose)-binding motif was found to overlap with five important functional domains responsible for protein-protein interactions, DNA binding, nuclear localization, nuclear export, and protein degradation, Thus, PARPs may target specific signal network proteins via poly(ADE)ribose and regulate their domain functions.
Journal ArticleDOI
Two Pathways for Base Excision Repair in Mammalian Cells
Guido Frosina,Paola Fortini,Ottavio Rossi,Fabio Carrozzino,Giuseppina Raspaglio,Lynne S. Cox,David P. Lane,Angelo Abbondandolo,Eugenia Dogliotti +8 more
TL;DR: Evidence is given that mammalian cell extracts repair natural AP sites by two distinct pathways: a single nucleotide gap filling reaction targeted at the AP site and a proliferating cell nuclear antigen-dependent pathway that removes a short oligonucleotide containing the abasic site and 3′-flanking nucleotides.
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Poly(ADP-ribosyl)ation of polynucleosomes causes relaxation of chromatin structure.
TL;DR: Poly(ADP-ribose) linked to histone H1 did not seem to cause its dissociation from the chromatin, but it impaired significantly its effect on chromatin condensation, resulting in a relaxed state of poly(ADp-ribosyl)ated polynucleosomes.
Journal ArticleDOI
Mutation of TDP1, encoding a topoisomerase I-dependent DNA damage repair enzyme, in spinocerebellar ataxia with axonal neuropathy.
Hiroshi Takashima,Cornelius F. Boerkoel,Joy John,Gulam Mustafa Saifi,Mustafa A. Salih,Dawna L. Armstrong,Yuxin Mao,Florante A. Quiocho,Benjamin B. Roa,Masanori Nakagawa,David W. Stockton,James R. Lupski +11 more
TL;DR: It is proposed that loss-of-function mutations in TDP1 may cause SCAN1 either by interfering with DNA transcription or by inducing apoptosis in postmitotic neurons.
Journal ArticleDOI
Base excision repair is impaired in mammalian cells lacking Poly(ADP-ribose) polymerase-1.
Françoise Dantzer,Guadelupe de la Rubia,Josiane Ménissier-de Murcia,Zdenek Hostomsky,and Gilbert de Murcia,Valérie Schreiber +5 more
TL;DR: Results show that PARP-1 is an active player in DNA base excision repair and demonstrates that DNA polymerase beta is involved in the repair of uracil-derived AP sites via both the short and the long-patch repair pathways.