Functional interrogation of DNA damage response variants with base editing screens
Mutations in DNA damage response (DDR) genes endanger genome integrity and
predispose to cancer and genetic disorders. Here, using CRISPR-dependent cytosine base …
predispose to cancer and genetic disorders. Here, using CRISPR-dependent cytosine base …
Revolutionizing DNA repair research and cancer therapy with CRISPR–Cas screens
All organisms possess molecular mechanisms that govern DNA repair and associated DNA
damage response (DDR) processes. Owing to their relevance to human disease, most …
damage response (DDR) processes. Owing to their relevance to human disease, most …
Paralog knockout profiling identifies DUSP4 and DUSP6 as a digenic dependence in MAPK pathway-driven cancers
Although single-gene perturbation screens have revealed a number of new targets,
vulnerabilities specific to frequently altered drivers have not been uncovered. An important …
vulnerabilities specific to frequently altered drivers have not been uncovered. An important …
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 …
TP53-dependent toxicity of CRISPR/Cas9 cuts is differential across genomic loci and can confound genetic screening
CRISPR/Cas9 gene editing can inactivate genes in a precise manner. This process involves
DNA double-strand breaks (DSB), which may incur a loss of cell fitness. We hypothesize that …
DNA double-strand breaks (DSB), which may incur a loss of cell fitness. We hypothesize that …
Double-strand break toxicity is chromatin context independent
Cells respond to double-strand breaks (DSBs) by activating DNA damage response
pathways, including cell cycle arrest. We have previously shown that a single double-strand …
pathways, including cell cycle arrest. We have previously shown that a single double-strand …
A genetic map of the response to DNA damage in human cells
M Olivieri, T Cho, A Álvarez-Quilón, K Li… - Cell, 2020 - cell.com
The response to DNA damage is critical for cellular homeostasis, tumor suppression,
immunity, and gametogenesis. In order to provide an unbiased and global view of the DNA …
immunity, and gametogenesis. In order to provide an unbiased and global view of the DNA …
Directed evolution using dCas9-targeted somatic hypermutation in mammalian cells
Engineering and study of protein function by directed evolution has been limited by the
technical requirement to use global mutagenesis or introduce DNA libraries. Here, we …
technical requirement to use global mutagenesis or introduce DNA libraries. Here, we …
[HTML][HTML] Genomic and molecular landscape of DNA damage repair deficiency across the cancer genome atlas
TA Knijnenburg, L Wang, MT Zimmermann… - Cell reports, 2018 - cell.com
DNA damage repair (DDR) pathways modulate cancer risk, progression, and therapeutic
response. We systematically analyzed somatic alterations to provide a comprehensive view …
response. We systematically analyzed somatic alterations to provide a comprehensive view …
Therapeutic opportunities within the DNA damage response
The DNA damage response (DDR) is essential for maintaining the genomic integrity of the
cell, and its disruption is one of the hallmarks of cancer. Classically, defects in the DDR have …
cell, and its disruption is one of the hallmarks of cancer. Classically, defects in the DDR have …