A well-accepted hallmark of
cancer is
genomic instability, which drives
tumorigenesis. Therefore, understanding the molecular and cellular defects that destabilize chromosomal integrity is paramount to
cancer diagnosis, treatment and cure. DNA repair and the replication stress response are overarching paradigms for maintenance of
genomic stability, but the devil is in the details.
ATP-dependent helicases serve to unwind
DNA so it is replicated, transcribed, recombined and repaired efficiently through coordination with other
nucleic acid binding and metabolizing
proteins. Alternatively folded
DNA structures deviating from the conventional anti-parallel double helix pose serious challenges to normal genomic transactions. Accumulating evidence suggests that G-quadruplex (G4)
DNA is problematic for replication. Although there are multiple human
DNA helicases that can resolve G4 in vitro, it is debated which helicases are truly important to resolve such structures in vivo. Recent advances have begun to elucidate the principal helicase actors, particularly in cellular DNA replication. FANCJ,
a DNA helicase implicated in
cancer and the
chromosomal instability disorder
Fanconi Anemia, takes center stage in G4 resolution to allow smooth DNA replication. We will discuss FANCJ's role with its
protein partner RPA to remove G4 obstacles during
DNA synthesis, highlighting very recent advances and implications for
cancer therapy.