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Mapping cellular responses to DNA double-strand breaks using CRISPR technologies. 2023

Yang Liu, and W Taylor Cottle, and Taekjip Ha
Department of Biophysics and Biophysical Chemistry, Johns Hopkins University, Baltimore, MD, USA.

DNA double-strand breaks (DSBs) are one of the most genotoxic DNA lesions, driving a range of pathological defects from cancers to immunodeficiencies. To combat genomic instability caused by DSBs, evolution has outfitted cells with an intricate protein network dedicated to the rapid and accurate repair of these lesions. Pioneering studies have identified and characterized many crucial repair factors in this network, while the advent of genome manipulation tools like clustered regularly interspersed short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) has reinvigorated interest in DSB repair mechanisms. This review surveys the latest methodological advances and biological insights gained by utilizing Cas9 as a precise 'damage inducer' for the study of DSB repair. We highlight rapidly inducible Cas9 systems that enable synchronized and efficient break induction. When combined with sequencing and genome-specific imaging approaches, inducible Cas9 systems greatly expand our capability to spatiotemporally characterize cellular responses to DSB at specific genomic coordinates, providing mechanistic insights that were previously unobtainable.

UI MeSH Term Description Entries
D004247 DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D004260 DNA Repair The removal of DNA LESIONS and/or restoration of intact DNA strands without BASE PAIR MISMATCHES, intrastrand or interstrand crosslinks, or discontinuities in the DNA sugar-phosphate backbones. DNA Damage Response
D000072669 Gene Editing Genetic engineering or molecular biology techniques that involve DNA REPAIR mechanisms for incorporating site-specific modifications into a cell's genome. Base Editing,Genome Editing,Editing, Base,Editing, Gene,Editing, Genome
D053903 DNA Breaks, Double-Stranded Interruptions in the sugar-phosphate backbone of DNA, across both strands adjacently. Double-Stranded DNA Breaks,Double-Strand DNA Breaks,Double-Stranded DNA Break,Break, Double-Strand DNA,Break, Double-Stranded DNA,Breaks, Double-Strand DNA,Breaks, Double-Stranded DNA,DNA Break, Double-Strand,DNA Break, Double-Stranded,DNA Breaks, Double Stranded,DNA Breaks, Double-Strand,Double Strand DNA Breaks,Double Stranded DNA Break,Double Stranded DNA Breaks,Double-Strand DNA Break
D059766 DNA End-Joining Repair The repair of DOUBLE-STRAND DNA BREAKS by rejoining the broken ends of DNA to each other directly. Non-Homologous DNA End-Joining,End-Joining DNA Repair,MMEJ DNA Repair,Microhomology-Mediated End Joining Repair,NHEJ DNA Repair,Nonhomologous DNA End-Joining,DNA End Joining Repair,DNA End-Joining, Non-Homologous,DNA End-Joining, Nonhomologous,DNA Repair, End-Joining,DNA Repair, MMEJ,DNA Repair, NHEJ,End Joining DNA Repair,End-Joining Repair, DNA,End-Joining, Non-Homologous DNA,Microhomology Mediated End Joining Repair,Non Homologous DNA End Joining,Nonhomologous DNA End Joining,Repair, DNA End-Joining,Repair, End-Joining DNA,Repair, MMEJ DNA,Repair, NHEJ DNA
D064113 CRISPR-Cas Systems Adaptive antiviral defense mechanisms, in archaea and bacteria, based on DNA repeat arrays called CLUSTERED REGULARLY INTERSPACED SHORT PALINDROMIC REPEATS (CRISPR elements) that function in conjunction with CRISPR-ASSOCIATED PROTEINS (Cas proteins). Several types have been distinguished, including Type I, Type II, and Type III, based on signature motifs of CRISPR-ASSOCIATED PROTEINS. CRISPR Cas Systems,CRISPR-Cas System,System, CRISPR-Cas,Systems, CRISPR-Cas

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