Spatial Dynamics of DNA Damage Response Protein Foci along the Ion Trajectory of High-LET Particles
Collection title:
Radiation Research
Journal:
Radiation Research
Volume:
176
Issue:
6
Year:
2011
Pages from - to:
706-715
Language:
Englisch
Keywords:
double stranded DNA ; gamma histone H2AX ; histone H2AX ; nuclear protein ; protein 53bp1 ; protein phospho nbs1 ; unclassified drug, algorithm ; article ; DNA damage ; double stranded DNA break ; human ; human cell ; immunofluorescence microscopy ; linear energy transfer ; molecular dynamics ; particle radiation ; priority journal ; protein structure, Algorithms ; Carbon ; Cell Cycle Proteins ; Computational Biology ; DNA Breaks, Double-Stranded ; DNA Damage ; Fibroblasts ; Histones ; Intracellular Signaling Peptides and Proteins ; Kinetics ; Linear Energy Transfer ; Models, Biological ; Nuclear Proteins ; Phosphoproteins ; Proteins ; Reproducibility of Results «
double stranded DNA ; gamma histone H2AX ; histone H2AX ; nuclear protein ; protein 53bp1 ; protein phospho nbs1 ; unclassified drug, algorithm ; article ; DNA damage ; double stranded DNA break ; human ; human cell ; immunofluorescence microscopy ; linear energy transfer ; molecular dynamics ; particle radiation ; priority journal ; protein structure, Algorithms ; Carbon ; Cell Cycle Proteins ; Computational Biology ; DNA Breaks, Double-Stranded ; DNA Damage ; Fibroblasts... »
Abstract:
High-linear energy transfer (LET) ion irradiation of cell nuclei induces complex and severe DNA lesions, and foci of repair proteins are formed densely along the ion trajectory. To efficiently discriminate the densely distributed/overlapping foci along the ion trajectory, a focus recognition algorithm called FociPicker3D based on a local fraction thresholding technique was developed. We analyzed high-resolution 3D immunofluorescence microscopic focus images and obtained the kinetics and spatial development of γ-H2AX, 53BP1 and phospho-NBS1 foci in BJ1-hTERT cells irradiated with 55 MeV carbon ions and compared the results with the dynamics of double-strand break (DSB) distributions simulated using the PARTRAC model. Clusters consisting of several foci were observed along the ion trajectory after irradiation. The spatial dynamics of the protein foci supports that the foci clusters are not formed by neighboring foci but instead originate from the DSB cluster damage induced by high-LET radiations. «
High-linear energy transfer (LET) ion irradiation of cell nuclei induces complex and severe DNA lesions, and foci of repair proteins are formed densely along the ion trajectory. To efficiently discriminate the densely distributed/overlapping foci along the ion trajectory, a focus recognition algorithm called FociPicker3D based on a local fraction thresholding technique was developed. We analyzed high-resolution 3D immunofluorescence microscopic focus images and obtained the kinetics and spatial... »