Article
A systematic CRISPR screen defines mutational mechanisms underpinning signatures caused by replication errors and endogenous DNA damage.
Nature cancer - 1 Jun 2021
Zou Xueqing, Koh Gene Ching Chiek, Nanda Arjun Scott, Degasperi Andrea, Urgo Katie, Roumeliotis Theodoros I, Agu Chukwuma A, Badja Cherif, Momen Sophie, Young Jamie, Amarante Tauanne Dias, Side Lucy, Brice Glen, Perez-Alonso Vanesa, Rueda Daniel, Gomez Celine, Bushell Wendy, Harris Rebecca, Choudhary Jyoti S, Jiricny Josef, Skarnes William C, Nik-Zainal Serena
Abstract excerpt
Mutational signatures are imprints of pathophysiological processes arising through tumorigenesis. We generated isogenic CRISPR-Cas9 knockouts (Δ) of 43 genes in human induced pluripotent stem cells, cultured them in the absence of added DNA damage, and performed whole-genome sequencing of 173 subclones. ΔOGG1, ΔUNG, ΔEXO1, ΔRNF168, ΔMLH1, ΔMSH2, ΔMSH6, ΔPMS1, and ΔPMS2 produced marked mutational signatures...
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