Cancers arise through the acquisition of oncogenic mutations and grow through clonal expansion 1,2 . Here we reveal that most mutagenic DNA lesions are not resolved as mutations within a single cell-cycle. Instead, DNA lesions segregate unrepaired into daughter cells for multiple cell generations, resulting in the chromosome-scale phasing of subsequent mutations. We characterise this process in mutagen-induced mouse liver tumours and show that DNA replication across persisting lesions can produce multiple alternative alleles in successive cell divisions, thereby generating both multi-allelic and combinatorial genetic diversity. The phasing of lesions enables the accurate measurement of strand biased repair processes, the quantification of oncogenic selection, and the fine mapping of sister chromatid exchange events. Finally, we demonstrate that lesion segregation is a unifying property of exogenous mutagens, including UV light and chemotherapy agents in human cells and tumours, which has profound implications for the evolution and adaptation of cancer genomes.
We show that the moduli space M X (v) of Gieseker stable sheaves on a smooth cubic threefold X with Chern character v = (3, −H, −H 2 /2, H 3 /6) is smooth and of dimension four. Moreover, the Abel-Jacobi map to the intermediate Jacobian of X maps it birationally onto the theta divisor Θ, contracting only a copy of X ⊂ M X (v) to the singular point 0 ∈ Θ.We use this result to give a new proof of a categorical version of the Torelli theorem for cubic threefolds, which says that X can be recovered from its Kuznetsov component Ku(X) ⊂ D b (X). Similarly, this leads to a new proof of the description of the singularity of the theta divisor, and thus of the classical Torelli theorem for cubic threefolds, i.e., that X can be recovered from its intermediate Jacobian.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.