Comprehensive Whole Genome Sequencing Reveals Origins of Mutational Signatures Associated with Aging and Temozolomide Chemotherapy
Taejoo Hwang,
Lukasz Karol Sitko,
Ratih Khoirunnisa
et al.
Abstract:In a comprehensive study to decipher the multi-layered response to the chemotherapeutic agent temozolomide (TMZ), we analyzed 427 genomes and determined mutational patterns in a collection of ~40 isogenic DNA repair-deficient human TK6 lymphoblast cell lines. We demonstrate that the spontaneous mutational background is very similar to the aging-associated mutational signature SBS40 and mainly caused by polymerase zeta-mediated translesion synthesis (TLS). MSH2-/- mismatch repair knockout in conjunction with ad… Show more
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