Z-form DNA-RNA hybrid blocks DNA replication

We discovered that the Z-form DNA-RNA hybrid stabilized by methylated CpG repeats impacts on the initiation and elongation of Okazaki fragments, contributing to blocking DNA replication at first time. We further present the first Z-form DNA-RNA hybrid structure by using NMR spectroscopy and dynamic computation, revealing the molecular mechanism of inhibition, indicating that a distinctive zig-zag strand pattern of the Z-form hybrid with a smaller helical diameter (15 Å) and a very narrow minor groove (8.3 Å) plays the key role in the repression toward DNA replication.