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
Aprataxin mutations are a rare cause of early onset ataxia in Germany.
Matthias Habeck,Christine Zühlke,Karl H P Bentele,Stephan Unkelbach,Wolfram Kreß,Katrin Bürk,Eberhard Schwinger,Yorck Hellenbroich +7 more
TL;DR: A group of 165 early onset ataxia patients were screened for APTX mutations and two non-related patients homozygous for the W293X nonsense mutation were detected, describing several new transcript variants of the APTX gene.
Journal ArticleDOI
E2F1 Regulates the Base Excision Repair Gene XRCC1 and Promotes DNA Repair
TL;DR: In this article, the XRCC1 promoter was cloned into a luciferase reporter to study the upstream mechanisms of the E2F1 transcription factor, which is important for efficient single strand break/base excision repair.
E2F1 Regulates the Base Excision Repair Gene XRCC1 and
TL;DR: The E2F1 transcription factor activates S-phase-promoting genes, mediates apoptosis, and stimulates DNA repair through incompletely understood mechanisms, and new mechanistic insight is provided into the role of the E 2F pathway in maintaining genomic stability.
Journal ArticleDOI
Poly(ADP-ribosylation) reduces the steady-state level of breaks in DNA following treatment of human cells with alkylating agents.
Alan R. Lehmann,B. C. Broughton +1 more
TL;DR: It is suggested that continued synthesis of poly(ADP-ribose) reduces the steady state level of breaks during excision repair of alkylation damage, which is probably mediated by the stimulation of DNA ligase activity.
Journal Article
Role for DNA polymerase beta in response to ionizing radiation
TL;DR: It is shown that mouse embryonic fibroblasts deficient in DNA polymerase beta are considerably more sensitive to ionizing radiation than wild-type cells, but only when confluent, the first evidence of a role for DNA polymerases beta in radiosensitivity in vivo.