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Twisting to the left. Twice

Researchers determine structure of Z-Z DNA junctions

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

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