WRN helicase is a synthetic lethal target in microsatellite unstable cancers

• Published in: Nature (London) Vol. 568; no. 7753; pp. 551 - 556
• Main Authors: Chan, Edmond M., Shibue, Tsukasa, McFarland, James M., Gaeta, Benjamin, Ghandi, Mahmoud, Dumont, Nancy, Gonzalez, Alfredo, McPartlan, Justine S., Li, Tianxia, Zhang, Yanxi, Bin Liu, Jie, Lazaro, Jean-Bernard, Gu, Peili, Piett, Cortt G., Apffel, Annie, Ali, Syed O., Deasy, Rebecca, Keskula, Paula, Ng, Raymond W. S., Roberts, Emma A., Reznichenko, Elizaveta, Leung, Lisa, Alimova, Maria, Schenone, Monica, Islam, Mirazul, Maruvka, Yosef E., Liu, Yang, Roper, Jatin, Raghavan, Srivatsan, Giannakis, Marios, Tseng, Yuen-Yi, Nagel, Zachary D., D’Andrea, Alan, Root, David E., Boehm, Jesse S., Getz, Gad, Chang, Sandy, Golub, Todd R., Tsherniak, Aviad, Vazquez, Francisca, Bass, Adam J.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.04.2019; Nature Publishing Group
• Subjects: 13; 13/2; 13/89; 14; 14/1; 14/19; 14/35; 38/39; 38/91; 42/41; 631/67/1059/602; 631/67/68; 631/67/69; 96/1; Adenosine diphosphate; Analysis; Apoptosis; Apoptosis - genetics; Biomarkers; Cancer; Cell cycle; Cell Cycle Checkpoints - genetics; Cell death; Cell Line, Tumor; CRISPR; CRISPR-Cas Systems - genetics; CRISPR-Cas technology; Datasets; Deoxyribonucleic acid; Dependence; Depletion; DNA; DNA Breaks, Double-Stranded; DNA damage; DNA helicase; DNA repair; Exonuclease; Gene expression; Genetic research; Genomes; Helicases; Homologous recombination; Homology; Humanities and Social Sciences; Humans; Instability; Kinases; Lethality; Letter; Microsatellite Instability; Microsatellite Repeats - genetics; Mismatch repair; Models, Genetic; multidisciplinary; Mutation; Neoplasms - genetics; Neoplasms - pathology; Poly(ADP-ribose); Poly(ADP-ribose) polymerase; RecQ protein; Repair; Ribose; RNA Interference; RNA-mediated interference; Science; Science (multidisciplinary); Stability; Stability analysis; Synthetic biology; Synthetic Lethal Mutations - genetics; Tumor Suppressor Protein p53 - metabolism; Werner syndrome; Werner Syndrome Helicase - deficiency; Werner Syndrome Helicase - genetics; United States > US

Synthetic lethality—an interaction between two genetic events through which the co-occurrence of these two genetic events leads to cell death, but each event alone does not—can be exploited for cancer therapeutics 1 . DNA repair processes represent attractive synthetic lethal targets, because many c...