A5020553867- CRISPR and Genetic Engineering
- Lung Cancer Research Studies
- Pneumocystis jirovecii pneumonia detection and treatment
- Genetic factors in colorectal cancer
- Cancer therapeutics and mechanisms
- Genomics and Chromatin Dynamics
- DNA Repair Mechanisms
University of Cambridge
2020-2023
The Gurdon Institute
2020-2023
Vlaams Instituut voor Biotechnologie
2020
CRISPR-Cas9 genome engineering has revolutionised high-throughput functional genomic screens. However, recent work raised concerns regarding the performance of screens using TP53 wild-type human cells due to a p53-mediated DNA damage response (DDR) limiting efficiency generating viable edited cells. To directly assess impact cellular p53 status on screen performance, we carried out parallel in and knockout retinal pigment epithelial focused dual guide RNA library targeting 852 DDR-associated...
The catalytic cycle of topoisomerase 2 (TOP2) enzymes proceeds via a transient DNA double-strand break (DSB) intermediate termed the TOP2 cleavage complex (TOP2cc), in which protein is covalently bound to DNA. Anticancer agents such as etoposide operate by stabilizing TOP2ccs, ultimately generating genotoxic TOP2-DNA cross-links that require processing and repair. Here, we identify RAD54 like (RAD54L2) factor promoting TOP2cc resolution. We demonstrate RAD54L2 acts through novel mechanism...