Journal ArticleDOI
Double-Strand Break End Resection and Repair Pathway Choice
TLDR
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.Abstract:
DNA double-strand breaks (DSBs) are cytotoxic lesions that can result in mutagenic events or cell death if left unrepaired or repaired inappropriately. Cells use two major pathways for DSB repair: nonhomologous end joining (NHEJ) and homologous recombination (HR). The choice between these pathways depends on the phase of the cell cycle and the nature of the DSB ends. A critical determinant of repair pathway choice is the initiation of 5′-3′ resection of DNA ends, which commits cells to homology-dependent repair, and prevents repair by classical NHEJ. Here, we review 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.read more
Citations
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Journal ArticleDOI
One-step generation of mice carrying mutations in multiple genes by CRISPR/Cas-mediated genome engineering.
Haoyi Wang,Hui Yang,Chikdu S. Shivalila,Meelad M. Dawlaty,Albert W. Cheng,Feng Zhang,Feng Zhang,Rudolf Jaenisch +7 more
TL;DR: The CRISPR/Cas system allows the one-step generation of animals carrying mutations in multiple genes, an approach that will greatly accelerate the in vivo study of functionally redundant genes and of epistatic gene interactions.
Journal ArticleDOI
CAS9 transcriptional activators for target specificity screening and paired nickases for cooperative genome engineering.
Prashant Mali,John Aach,P. Benjamin Stranges,Kevin M. Esvelt,Mark Moosburner,Sriram Kosuri,Luhan Yang,George M. Church,George M. Church +8 more
TL;DR: This system is engineer to enable RNA-guided genome regulation in human cells by tethering transcriptional activation domains either directly to a nuclease-null Cas9 protein or to an aptamer-modified single guide RNA (sgRNA).
Journal ArticleDOI
Simultaneous editing of three homoeoalleles in hexaploid bread wheat confers heritable resistance to powdery mildew
TL;DR: It is shown that TALEN-induced mutation of all three TaMLO homoeologs in the same plant confers heritable broad-spectrum resistance to powdery mildew, and provides a methodological framework to improve polyploid crops.
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
Repair Pathway Choices and Consequences at the Double-Strand Break
TL;DR: Alternative error-prone DSB repair pathways, namely alternative end joining (alt-EJ) and single-strand annealing (SSA) have been recently shown to operate in many different conditions and to contribute to genome rearrangements and oncogenic transformation.
References
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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
ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage
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TL;DR: A large-scale proteomic analysis of proteins phosphorylated in response to DNA damage on consensus sites recognized by ATM and ATR is performed and more than 900 regulated phosphorylation sites encompassing over 700 proteins are identified.
Journal ArticleDOI
Sensing DNA Damage Through ATRIP Recognition of RPA-ssDNA Complexes
Lee Zou,Stephen J. Elledge +1 more
TL;DR: The data suggest that RPA-coated ssDNA is the critical structure at sites of DNA damage that recruits the ATR-ATRIP complex and facilitates its recognition of substrates for phosphorylation and the initiation of checkpoint signaling.
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
Multiple Pathways of Recombination Induced by Double-Strand Breaks in Saccharomyces cerevisiae
Frédéric Pâques,James E. Haber +1 more
TL;DR: This review encompasses different aspects of DSB-induced recombination in Saccharomyces and attempts to relate genetic, molecular biological, and biochemical studies of the processes of DNA repair and recombination.