Nanomechanical Fingerprints of Gamma Radiation Damage to DNA
The exposure of cancer cells to ionizing radiation results in potentially lethal DNA lesions. For this reason, identification and quantification of various lesions have intensively been investigated. It has also been anticipated that DNA lesions may affect not only the chemical but
also the mechanical integrity of the double helix. However, the relationship between DNA damage and mechanics has not been studied. Here, the mechanical properties of DNA damaged by ionizing radiation are examined at a single-molecule level by stretching λ-phage DNA molecules
that have been exposed to λ-radiation. A simple-stretching method using Atomic Force Microscopy (AFM) not only identifies the types of DNA lesions but also provides information about the mechanical instability of damaged DNA against intact DNA. The results include the elastic
properties of damaged DNA with single strand breaks (SSBs), double strand breaks (DSBs), and multiple-lesion clusters. The elasticity of irradiated DNA is changed compared to that of intact DNA. Specifically, consecutive stretching cycles of DNA containing multiple SSBs progressively shorten
the width of the overstretching B-S transition. This originates from force-induced melting off of single-stranded DNA fragments, which upon consecutive stretching cycles converts the double helix into a hybrid structure with a growing number of single stranded gaps. Closely spaced SSBs on
opposite strands, upon stretching, result in a rupture of the double helix at a decreased force of approximately 200 pN and other clustered lesions result in lowering the force at which force-induced melting of the double helix occurs. Taken together, our results suggest that single-molecule
force spectroscopy may become a useful nanoscale DNA diagnostic tool.
Keywords: AFM; DNA ELASTICITY; DNA LESIONS; GAMMA-RAY; SINGLE MOLECULE FORCE SPECTROSCOPY
Document Type: Research Article
Publication date: 01 December 2009
- Journal for Nanoscience and Nanotechnology (JNN) is an international and multidisciplinary peer-reviewed journal with a wide-ranging coverage, consolidating research activities in all areas of nanoscience and nanotechnology into a single and unique reference source. JNN is the first cross-disciplinary journal to publish original full research articles, rapid communications of important new scientific and technological findings, timely state-of-the-art reviews with author's photo and short biography, and current research news encompassing the fundamental and applied research in all disciplines of science, engineering and medicine.
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