Fig. 5: Proposed mechanism for Z-DNA-induced genetic instability in eukaryotes.
From: Distinct DNA repair pathways cause genomic instability at alternative DNA structures
During DNA metabolic processes, the CG repeat sequence is unwrapped from histones (blue circles) and negative supercoiling is generated, which stimulates Z-DNA formation. The structure of Z-DNA is recognized as “damage” by the MSH2-MSH3 complex, signaling repair. The ERCC1-XPF complex is recruited to the site for cleavage near the Z-DNA-forming region (processing of the B-Z junction on the right side of Z-DNA is shown in the figure; however, similar processing could also occur at the other B-Z junction on the left, marked as a scissor), resulting in DSBs in an attempt to repair the “damage”. The breaks may be processed in an error-free fashion, or the breaks may be processed in an error-generating fashion resulting in genomic instability in the form of large deletions and translocations, which may contribute to disease etiology.
