A systematic CRISPR screen defines mutational mechanisms underpinning signatures caused by replication errors and endogenous DNA damage
Mutational signatures are imprints of pathophysiological processes arising through
tumorigenesis. We generated isogenic CRISPR–Cas9 knockouts (∆) of 43 genes in human …
tumorigenesis. We generated isogenic CRISPR–Cas9 knockouts (∆) of 43 genes in human …
Use of CRISPR-modified human stem cell organoids to study the origin of mutational signatures in cancer
Mutational processes underlie cancer initiation and progression. Signatures of these
processes in cancer genomes may explain cancer etiology and could hold diagnostic and …
processes in cancer genomes may explain cancer etiology and could hold diagnostic and …
Genomic copy number dictates a gene-independent cell response to CRISPR/Cas9 targeting
The CRISPR/Cas9 system enables genome editing and somatic cell genetic screens in
mammalian cells. We performed genome-scale loss-of-function screens in 33 cancer cell …
mammalian cells. We performed genome-scale loss-of-function screens in 33 cancer cell …
Unbiased detection of CRISPR off-targets in vivo using DISCOVER-Seq
CRISPR-Cas genome editing induces targeted DNA damage but can also affect off-target
sites. Current off-target discovery methods work using purified DNA or specific cellular …
sites. Current off-target discovery methods work using purified DNA or specific cellular …
p53 inhibits CRISPR–Cas9 engineering in human pluripotent stem cells
CRISPR/Cas9 has revolutionized our ability to engineer genomes and conduct genome-
wide screens in human cells,–. Whereas some cell types are amenable to genome …
wide screens in human cells,–. Whereas some cell types are amenable to genome …
Sequential CRISPR gene editing in human iPSCs charts the clonal evolution of myeloid leukemia and identifies early disease targets
Human cancers arise through the sequential acquisition of somatic mutations that create
successive clonal populations. Human cancer evolution models could help illuminate this …
successive clonal populations. Human cancer evolution models could help illuminate this …
CRISPR/Cas9-induced DNA damage enriches for mutations in a p53-linked interactome: implications for CRISPR-based therapies
Inactivating p53 mutations are the most abundant genetic alterations found in cancer. Here
we show that CRISPR/Cas9-induced double-stranded DNA breaks enrich for cells deficient …
we show that CRISPR/Cas9-induced double-stranded DNA breaks enrich for cells deficient …
Validating the concept of mutational signatures with isogenic cell models
The diversity of somatic mutations in human cancers can be decomposed into individual
mutational signatures, patterns of mutagenesis that arise because of DNA damage and DNA …
mutational signatures, patterns of mutagenesis that arise because of DNA damage and DNA …
CIRCLE-seq: a highly sensitive in vitro screen for genome-wide CRISPR–Cas9 nuclease off-targets
Sensitive detection of off-target effects is important for translating CRISPR–Cas9 nucleases
into human therapeutics. In vitro biochemical methods for finding off-targets offer the …
into human therapeutics. In vitro biochemical methods for finding off-targets offer the …
Computational correction of copy number effect improves specificity of CRISPR–Cas9 essentiality screens in cancer cells
The CRISPR–Cas9 system has revolutionized gene editing both at single genes and in
multiplexed loss-of-function screens, thus enabling precise genome-scale identification of …
multiplexed loss-of-function screens, thus enabling precise genome-scale identification of …