title: Spatial dynamics of DNA damage response protein foci along the ion trajectory of high-LET particles.
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.
authors.affiliation: Physik Department E12, Technische Universität München, 85748 Garching, Germany. gh_du@impcas.ac.cn
authors.forename: Guanghua
authors.initials: G
authors.lastname: Du
authors.forename: Guido A
authors.initials: GA
authors.lastname: Drexler
authors.forename: Werner
authors.initials: W
authors.lastname: Friedland
authors.forename: Christoph
authors.initials: C
authors.lastname: Greubel
authors.forename: Volker
authors.initials: V
authors.lastname: Hable
authors.forename: Reiner
authors.initials: R
authors.lastname: Krücken
authors.forename: Alexandra
authors.initials: A
authors.lastname: Kugler
authors.forename: Laura
authors.initials: L
authors.lastname: Tonelli
authors.forename: Anna A
authors.initials: AA
authors.lastname: Friedl
authors.forename: Günther
authors.initials: G
authors.lastname: Dollinger
mesh_terms: D000465:Algorithms; D002244:Carbon; D018797:Cell Cycle Proteins / Q000378:metabolism; D019295:Computational Biology / Q000379:methods*; D053903:DNA Breaks, Double-Stranded / Q000528:radiation effects; D004249:DNA Damage; D005347:Fibroblasts / Q000378:metabolism / Q000528:radiation effects; D006657:Histones / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D007700:Kinetics; D018499:Linear Energy Transfer; D008954:Models, Biological; D009687:Nuclear Proteins / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D015203:Reproducibility of Results; D000071857:Tumor Suppressor p53-Binding Protein 1
chemical_list: D018797:Cell Cycle Proteins; C468783:H2AX protein, human; D006657:Histones; D047908:Intracellular Signaling Peptides and Proteins; C112156:NBN protein, human; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011506:Proteins; C498301:TP53BP1 protein, human; D000071857:Tumor Suppressor p53-Binding Protein 1; D002244:Carbon