Z-DNA

Z-DNA-forming sequences generate large-scale deletions in mammalian cells tells of a condition that is associated with increased likelihood of genetic instability and incurrence of specific diseases. The condition- spontaneous chromosomal breakages- has been known to occur with greater frequency in genomic hot spots. These chromosomal breakpoints in turn are frequently found near Z-DNA forming sequences.

"There are three major structural forms of DNA; the B form, described by Watson and Crick in 1953, the A form and the Z form... Z-DNA is a left-handed helix that contains about twelve base pairs per turn... Transitions between the helical forms of DNA may play an important role in regulating gene expression."1

In mammalian cells, the Z-DNA-forming sequences induce double-strand breaks nearby, resulting in large-scale deletions in 95% of the mutants... Our data suggest that Z-DNA-forming sequences may be causative factors for gene translocations found in leukemias and lymphomas and that certain cellular conditions such as active transcription may increase the risk of Z-DNA-related genetic instability... Chromosomal translocations leading to carcinogenesis may be associated with normal metabolic processes as well as DNA damage caused by endogenous or environmental genotoxic agents.

The article notes that homologous recombination, which can lead to DNA repair, is induced by the formation of Z-DNA. It also indicates a conclusion that processing of Z-DNA by repair mechanisms in mammals can incur large-scale genomic rearrangements and deletions. A general theme of this blog is highlighting the central importance of DNA repair to the viability of life. DNA repair is varied and extensive. Z-DNA is another chapter of the story.


References:

1. Biochemistry 3rd edition; Pamela C. Champe, Richard A. Harvey and Denise R. Ferrier; Lippencott Williams & Wilkins; Page 396.

2. Z-DNA-forming sequences generate large-scale deletions in mammalian cells; PNAS | February 21, 2006 | vol. 103 | no. 8 | 2677-2682; Guliang Wang, Laura A. Christensen, and Karen M. Vasquez