Noncanonical views of homology-directed DNA repair
TLDR
How alternative HDR pathways in both prokaryotes and eukaryotes in different contexts are executed is reviewed, specifically focusing on the determinants that dictate competition between them and their relevance to cancers that display complex genomic rearrangements or maintain their telomeres by homology-directed DNA synthesis.Abstract:
DNA repair is essential to maintain genomic integrity and initiate genetic diversity. While gene conversion and classical nonhomologous end-joining are the most physiologically predominant forms of DNA repair mechanisms, emerging lines of evidence suggest the usage of several noncanonical homology-directed repair (HDR) pathways in both prokaryotes and eukaryotes in different contexts. Here we review how these alternative HDR pathways are executed, specifically focusing on the determinants that dictate competition between them and their relevance to cancers that display complex genomic rearrangements or maintain their telomeres by homology-directed DNA synthesis.read more
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Applications of genome editing technology in the targeted therapy of human diseases: mechanisms, advances and prospects
TL;DR: Recent advances of the three major genome editing technologies are reviewed and the applications of their derivative reagents as gene editing tools in various human diseases and potential future therapies are discussed, focusing on eukaryotic cells and animal models.
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The control of DNA repair by the cell cycle
TL;DR: How DNA repair processes, and DNA double-strand break repair in particular, are regulated during the cell cycle to optimize genomic integrity is reviewed.
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Break-induced telomere synthesis underlies alternative telomere maintenance
Robert L. Dilley,Priyanka Verma,Nam Woo Cho,Harrison D. Winters,Anne R. Wondisford,Roger A. Greenberg +5 more
TL;DR: The inception of telomere damage recognition by the break-induced replisome orchestrates homology-directed telomeres maintenance, which underlies ALT telitere maintenance.
Journal ArticleDOI
Advances in genome editing through control of DNA repair pathways.
TL;DR: This Review discusses the DNA repair pathways that underlie genome editing and recent improvements and strategies to yield desired genomic alterations in cells and organisms.
Journal ArticleDOI
Inhibition of 53BP1 favors homology-dependent DNA repair and increases CRISPR-Cas9 genome-editing efficiency.
Marella D. Canny,Nathalie Moatti,Leo C. K. Wan,Leo C. K. Wan,Amélie Fradet-Turcotte,Amélie Fradet-Turcotte,Danielle Krasner,Pedro A. Mateos-Gómez,Michal Zimmermann,Alexandre Orthwein,Alexandre Orthwein,Yu-Chi Juang,Wei Zhang,Sylvie M. Noordermeer,Eduardo Seclén,Marcus D. Wilson,Andrew Vorobyov,Meagan Munro,Andreas Ernst,Andreas Ernst,Timothy F. Ng,Timothy F. Ng,Tiffany Cho,Tiffany Cho,Paula M. Cannon,Sachdev S. Sidhu,Frank Sicheri,Frank Sicheri,Daniel Durocher,Daniel Durocher +29 more
TL;DR: expression of one variant, named i53 (inhibitor of 53BP1), in human and mouse cells, blocked accumulation of 53 BP1 at sites of DNA damage and improved gene targeting and chromosomal gene conversion with either double-stranded DNA or single-strander oligonucleotide donors by up to 5.6-fold.
References
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Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy
Hannah Farmer,Nuala McCabe,Christopher J. Lord,Andrew Tutt,Andrew Tutt,Damian A. Johnson,Tobias B. Richardson,Manuela Santarosa,Krystyna J. Dillon,Ian Hickson,Charlotte Knights,Niall M. B. Martin,Stephen P. Jackson,Graeme C. M. Smith,Alan Ashworth +14 more
TL;DR: BRCA1 or BRCA2 dysfunction unexpectedly and profoundly sensitizes cells to the inhibition of PARP enzymatic activity, resulting in chromosomal instability, cell cycle arrest and subsequent apoptosis, illustrating how different pathways cooperate to repair damage.
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Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase
Helen E. Bryant,Nilklas Schultz,Huw D. Thomas,Kayan M. Parker,Dan Flower,Elena Lopez,Suzanne Kyle,Mark Meuth,Nicola J. Curtin,Thomas Helleday,Thomas Helleday +10 more
TL;DR: It is proposed that, in the absence of PARP1, spontaneous single-strand breaks collapse replication forks and trigger homologous recombination for repair and exploited in order to kill BRCA2-deficient tumours by PARP inhibition alone.
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A survey of telomerase activity in human cancer
Jerry W. Shay,Silvia Bacchetti +1 more
TL;DR: All major types of cancer have been screened and the presence of telomerase activity has been detected in the vast majority of cases, and a summary, in table form, of the current data is provided.
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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.
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Mammalian Telomeres End in a Large Duplex Loop
Jack D. Griffith,Laurey Comeau,Soraya Rosenfield,Rachel M. Stansel,Alessandro Bianchi,Heidi Moss,Titia de Lange +6 more
TL;DR: Electron microscopy reported here demonstrated that TRF2 can remodel linear telomeric DNA into large duplex loops (t loops) in vitro, which may provide a general mechanism for the protection and replication of telomeres.