Twisting to the left. Twice

Oeiras, 21.05.10

The helix in DNA can be made twisting the strands to the right or to the left. Nature has both but the presence of left-handed DNA has been linked to cancer. Researchers at ITQB (X-ray Crystalography Unit), IGC and MIT analysed the junction points between two left-handed helixes and found enough room for mutagenic agents to insert themselves. Results were published in the Proceedings of the National Academy of Sciences.

Naturally occurring DNA is mostly right-handed (called the B-form) but evidence for the in vivo existence of left-handed DNA (called the Z-form) is growing. A single DNA molecule can have both forms and the transition zones (called B-Z junction), resulting in exposed nucleotides, are known to be chemically vulnerable. Resorting to X-ray crystallography researchers visualized a related scenario for Z-Z junctions - when a left-handed helix is interrupted - but in this case no nucleotides are exposed. Instead, the helical stacking is disrupted, creating a site for intercalation. Researchers suggest that this site can also be a target for anticancer drugs.

Original Article

Published online before print May 3, 2010, doi: 10.1073/pnas.1003182107

Crystal structure of a junction between two Z-DNA helices

Matteo de Rosa, Daniele de Sanctis, Ana Lucia Rosario, Margarida Archer, Alexander Rich, Alekos Athanasiadis, and Maria Armenia Carrondo

IGC - Matteo de Rosa and Alekos Athanasiadis (corresponding author); ITQB - Matteo de Rosa, Ana Lucia Rosario, Margarida Archer, and Maria Armenia Carrondo; MIT - Alexander Rich; ESRF -  Daniele de Sanctis