Mounting evidence indicates that alternate
DNA structures, which deviate from normal double helical
DNA, form in vivo and influence cellular processes such as replication and transcription. However, our understanding of how the cellular machinery deals with unusual
DNA structures such as G-quadruplexes (G4), triplexes, or hairpins is only beginning to emerge. New advances in the field implicate a direct role of the
Fanconi Anemia Group J (FANCJ) helicase, which is linked to a hereditary
chromosomal instability disorder and important for
cancer suppression, in replication past unusual
DNA obstacles. This work sets the stage for significant progress in dissecting the molecular mechanisms whereby replication perturbation by abnormal
DNA structures leads to
genomic instability. In this review, we focus on FANCJ and its role to enable efficient DNA replication when the fork encounters vastly abundant naturally occurring
DNA obstacles, which may have implications for targeting rapidly dividing
cancer cells.