Journal ArticleDOI
Double-strand break repair: 53BP1 comes into focus
TLDR
A model is emerging in which 53BP1 recruitment requires the direct recognition of a DSB-specific histone code and its influence on pathway choice is mediated by mutual antagonism with breast cancer 1 (BRCA1).Abstract:
DNA double-strand break (DSB) signalling and repair is crucial to preserve genomic integrity and maintain cellular homeostasis. p53-binding protein 1 (53BP1) is an important regulator of the cellular response to DSBs that promotes the end-joining of distal DNA ends, which is induced during V(D)J and class switch recombination as well as during the fusion of deprotected telomeres. New insights have been gained into the mechanisms underlying the recruitment of 53BP1 to damaged chromatin and how 53BP1 promotes non-homologous end-joining-mediated DSB repair while preventing homologous recombination. From these studies, a model is emerging in which 53BP1 recruitment requires the direct recognition of a DSB-specific histone code and its influence on pathway choice is mediated by mutual antagonism with breast cancer 1 (BRCA1).read more
Citations
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Increasing the efficiency of precise genome editing with CRISPR-Cas9 by inhibition of nonhomologous end joining
Takeshi Maruyama,Stephanie K. Dougan,Matthias C. Truttmann,Angelina M. Bilate,Jessica R. Ingram,Hidde L. Ploegh +5 more
TL;DR: In this article, the authors targeted DNA ligase IV, a key enzyme in the NHEJ pathway, using the inhibitor Scr7, which increased the efficiency of HDR-mediated genome editing, using Cas9 in mammalian cell lines and in mice for all four genes examined.
Journal ArticleDOI
Mechanisms of DNA damage, repair, and mutagenesis.
TL;DR: This introductory review will delineate mechanisms of DNA damage and the counteracting repair/tolerance pathways to provide insights into the molecular basis of genotoxicity in cells that lays the foundation for subsequent articles in this issue.
Journal ArticleDOI
NRF2 and the Hallmarks of Cancer.
TL;DR: The roles of NRF2 in the hallmarks of cancer are explored, indicating both tumor suppressive and tumor-promoting effects.
Journal ArticleDOI
The Shieldin complex mediates 53BP1-dependent DNA repair
Sylvie M. Noordermeer,Sylvie M. Noordermeer,Salomé Adam,Dheva Setiaputra,Marco Barazas,Stephen J. Pettitt,Alexanda K. Ling,Michele Olivieri,Michele Olivieri,Alejandro Álvarez-Quilón,Nathalie Moatti,Michal Zimmermann,Stefano Annunziato,Dragomir B. Krastev,Feifei Song,Inger Brandsma,Jessica Frankum,Rachel Brough,Alana Sherker,Alana Sherker,Sébastien Landry,Rachel K. Szilard,Meagan Munro,Andrea McEwan,Theo Goullet de Rugy,Zhen-Yuan Lin,Traver Hart,Jason Moffat,Anne-Claude Gingras,Anne-Claude Gingras,Alberto Martin,Haico van Attikum,Jos Jonkers,Christopher J. Lord,Sven Rottenberg,Sven Rottenberg,Daniel Durocher,Daniel Durocher +37 more
TL;DR: The 53 BP1 effector complex shieldin is involved in non-homologous end-joining and immunoglobulin class switching, and acts to protect DNA ends to facilitate the repair of DNA by 53BP1, it is shown that binding of single-stranded DNA by SHLD2 is critical for shieldin function.
Journal ArticleDOI
Non-histone protein methylation as a regulator of cellular signalling and function
Kyle K. Biggar,Shawn S.-C. Li +1 more
TL;DR: The stage is now set to decode the methylproteome and define its functions in health and disease with recent advances in proteomic techniques.
References
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Journal ArticleDOI
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 Mechanism of Double-Strand DNA Break Repair by the Nonhomologous DNA End-Joining Pathway
TL;DR: Patients lacking normal NHEJ are not only sensitive to ionizing radiation (IR), but also severely immunodeficient in the range of DNA end substrate configurations upon which they can act.
Journal ArticleDOI
53BP1 Inhibits Homologous Recombination in Brca1-Deficient Cells by Blocking Resection of DNA Breaks
Samuel F. Bunting,Elsa Callen,Nancy Wong,Hua Tang Chen,Federica Polato,Amanda Gunn,Anne Bothmer,Niklas Feldhahn,Oscar Fernandez-Capetillo,Liu Cao,Xiaoling Xu,Chu-Xia Deng,Toren Finkel,Michel C. Nussenzweig,Michel C. Nussenzweig,Jeremy M. Stark,André Nussenzweig +16 more
TL;DR: It is shown that DNA breaks in Brca1-deficient cells are aberrantly joined into complex chromosome rearrangements by a process dependent on the nonhomologous end-joining (NHEJ) factors 53BP1 and DNA ligase 4, illustrating that HR and NHEJ compete to process DNA breaks that arise during DNA replication.
Journal ArticleDOI
Playing the End Game: DNA Double-Strand Break Repair Pathway Choice
TL;DR: Recent insights are reviewed into the mechanisms that influence the choice between competing DSB repair pathways, how this is regulated during the cell cycle, and how imbalances in this equilibrium result in genome instability.
Journal ArticleDOI
Double-Strand Break End Resection and Repair Pathway Choice
TL;DR: The components of the end resection machinery, the role of end structure, and the cell-cycle phase on resection and the interplay of end processing with NHEJ are reviewed.