Journal ArticleDOI
The control of DNA repair by the cell cycle
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TLDR
How DNA repair processes, and DNA double-strand break repair in particular, are regulated during the cell cycle to optimize genomic integrity is reviewed.Abstract:
The correct duplication and transmission of genetic material to daughter cells is the primary objective of the cell division cycle. DNA replication and chromosome segregation present both challenges and opportunities for DNA repair pathways that safeguard genetic information. As a consequence, there is a profound, two-way connection between DNA repair and cell cycle control. Here, we review how DNA repair processes, and DNA double-strand break repair in particular, are regulated during the cell cycle to optimize genomic integrity.read more
Citations
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Journal ArticleDOI
ATM, ATR, and DNA-PK: The Trinity at the Heart of the DNA Damage Response.
TL;DR: A historical perspective of their discovery is provided and their established functions in sensing and responding to genotoxic stress are discussed, as well as emerging non-canonical roles and how knowledge of ATM, ATR, and DNA-PK is being translated to benefit human health.
Journal ArticleDOI
CRISPR-Cas9 genome editing induces a p53-mediated DNA damage response.
Emma Haapaniemi,Emma Haapaniemi,Sandeep Kumar Botla,Jenna Persson,Bernhard Schmierer,Jussi Taipale,Jussi Taipale,Jussi Taipale +7 more
TL;DR: It is reported that genome editing by CRISPR–Cas9 induces a p53-mediated DNA damage response and cell cycle arrest in immortalized human retinal pigment epithelial cells, leading to a selection against cells with a functional p53 pathway, suggesting that p53 inhibition may improve the efficiency of genome editing of untransformed cells.
Journal ArticleDOI
Homologous recombination and the repair of DNA Double-Strand Breaks
TL;DR: The DNA transactions and enzymatic activities required for this elegantly orchestrated process in the context of the repair of DNA double-strand breaks in somatic cells are discussed.
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
DNA Repair Network Analysis Reveals Shieldin as a Key Regulator of NHEJ and PARP Inhibitor Sensitivity
Rajat Gupta,Kumar Somyajit,Takeo Narita,Elina Maskey,Andre Stanlie,Magdalena Kremer,Dimitris Typas,Michael Lammers,Michael Lammers,Niels Mailand,André Nussenzweig,Jiri Lukas,Chunaram Choudhary +12 more
TL;DR: This work generated high-resolution interaction neighborhood maps of the endogenously expressed DNA repair factors 53BP1, BRCA1, and MDC1 and identified a novel vertebrate-specific protein complex, shieldin, comprising REV7 plus three previously uncharacterized proteins, RINN1 (CTC-534A2.2), RINn2 (FAM35A), and RinN3 (C20ORF196).
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
Megabase chromatin domains involved in DNA double-strand breaks in vivo.
TL;DR: The results offer direct visual confirmation that γ-H2AX forms en masse at chromosomal sites of DNA double-strand breaks and suggest the possible existence of units of higher order chromatin structure involved in monitoring DNA integrity.
Journal ArticleDOI
Causes and consequences of replication stress.
TL;DR: In this paper, the kinase ATR (ATM- and Rad3-related) stabilizes and helps to restart stalled replication forks, avoiding the generation of DNA damage and genome instability.
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.