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Over the last three decades, evidence has emerged that low-intensity magnetic fields can influence biological systems. It is now well established that migratory birds have the capacity to detect the Earth's magnetic field; it has been reported that power lines are associated with childhood leukemia and that pulsed magnetic fields increase the production of reactive oxidative species (ROS) in cellular systems. Justifiably, studies in this field have been viewed with skepticism, as the underlying molecular mechanisms are unknown. In the accompanying paper, Sherrard and colleagues report that low-flux pulsed electromagnetic fields (PEMFs) result in aversive behavior in Drosophila larvae and ROS production in cell culture. They further report that these responses require the presence of cryptochrome, a putative magnetoreceptor. If correct, it is conceivable that carcinogenesis associated with power lines, PEMF-induced ROS generation, and animal magnetoreception share a common mechanistic basis. [ABSTRACT FROM AUTHOR]

A single cancer genome can harbor thousands of clustered mutations. Mutation signature analyses have revealed that the origin of clusters are lesions in long tracts of single-stranded (ss) DNA damaged by apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC) cytidine deaminases, raising questions about molecular mechanisms that generate long ssDNA vulnerable to hypermutation. Here, we show that ssDNA intermediates formed during the repair of gamma-induced bursts of double-strand breaks (DSBs) in the presence of APOBEC3A in yeast lead to multiple APOBEC-induced clusters similar to cancer. We identified three independent pathways enabling cluster formation associated with repairing bursts of DSBs: 5′ to 3′ bidirectional resection, unidirectional resection, and break-induced replication (BIR). Analysis of millions of mutations in APOBEC-hypermutated cancer genomes revealed that cancer tolerance to formation of hypermutable ssDNA is similar to yeast and that the predominant pattern of clustered mutagenesis is the same as in resection-defective yeast, suggesting that cluster formation in cancers is driven by a BIR-like mechanism. The phenomenon of genome-wide burst of clustered mutagenesis revealed by our study can play an important role in generating somatic hypermutation in cancers as well as in noncancerous cells. [ABSTRACT FROM AUTHOR]