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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Journal ArticleDOI
DNA Ligases I and III Cooperate in Alternative Non-Homologous End-Joining in Vertebrates
Katja Paul,Minli Wang,Emil Mladenov,Alena Bencsik-Theilen,Theresa Bednar,Wenqi Wu,Hiroshi Arakawa,George Iliakis +7 more
TL;DR: A remarkable ability for LIG3 to backup DSB repair by NHEJ in addition to its essential function in the mitochondria is demonstrated and uncovered, uncovering a remarkable and previously unappreciated functional flexibility and interchangeability between LIG1 and Lig3.
Journal ArticleDOI
PARP regulates nonhomologous end joining through retention of Ku at double-strand breaks
C. Anne-Marie Couto,Hong-Yu Wang,Joanna C.A. Green,Rhian Kiely,Robert Siddaway,Christine Borer,Catherine J. Pears,Nicholas D. Lakin +7 more
TL;DR: Poly ADP-ribosylation polymerases are necessary for recruitment and/or retention of Ku at double-strand breaks during nonhomologous end-joining DNA repair.
Journal ArticleDOI
Development of hRad51-Cas9 nickase fusions that mediate HDR without double-stranded breaks.
Holly A. Rees,Holly A. Rees,Holly A. Rees,Wei-Hsi Yeh,David R. Liu,David R. Liu,David R. Liu +6 more
TL;DR: HRad51 mutants fused to Cas9(D10A) nickase (RDN) that mediate HDR while minimizing indels are developed that provide precision editing options in cell types amenable to HDR, especially when byproducts of DSBs must be minimized.
Journal ArticleDOI
Recognition and repair of chemically heterogeneous structures at DNA ends.
TL;DR: An overview of cellular first responders dedicated to the detection and repair of abnormal DNA termini is provided to prevent genomic instability and disease, and promote progression of DNA‐ and RNA‐DNA damage response pathways.
Posted ContentDOI
Neuronal Enhancers are Hotspots For DNA Single-Strand Break Repair
Wei Wu,Sarah E. Hill,William J. Nathan,Jacob Paiano,Kenta Shinoda,Jennifer M. Colón-Mercado,Elsa Callen,Raffaella De Pace,Dongpeng Wang,Han-Yu Shih,Steve Coon,Maia Parsadanian,Hana Hanzlikova,Hana Hanzlikova,Peter J. McHugh,Andres Canela,Keith W. Caldecott,Keith W. Caldecott,Michael E. Ward,André Nussenzweig +19 more
TL;DR: It is shown that neurons, but not other post-mitotic cells, accumulate unexpectedly high numbers of DNA single-strand breaks (SSBs) at specific sites within the genome, suggesting an explanation for the neurodegenerative phenotypes that occur in patients with defective SSB repair.
References
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Journal ArticleDOI
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Journal ArticleDOI
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