title: DNA damage recognition proteins localize along heavy ion induced tracks in the cell nucleus.
abstract: To identify the repair dynamics involved in high linear energy transfer (LET) radiation-induced DNA damage, phospho-H2AX (gammaH2AX) foci formation was analyzed after cellular exposure to iron ions (Fe-ions, 500 MeV u(-1), 200 KeV microm(-1)). The foci located at DNA damage sites were visualized using immunocytochemical methods. Since H2AX is phosphorylated at sites of radiation-induced double strand breaks (DSB), gammaH2AX foci were used to detect or illuminate tracks formed by DSB after exposure to various doses of ionizing radiation. Additional DSB-recognition proteins such as ATM phospho-serine 1981, DNA-PKcs phospho-threonine 2609, NBS1 phospho-serine 343 and CHK2 phospho-threonine 68 all co-localized with gammaH2AX at high LET radiation induced DSB. In addition, Fe-ion induced foci remained for longer times than X-radiation induced foci. These findings suggest that Fe-ion induced damage is repaired more slowly than X-radiation induced damage, possibly because Fe-ion induced damage or lesions are more complex or extensive. Antibodies for all these phosphorylated DNA DSB recognition proteins appear to be very effective for the detection and localization of DSB.
authors.affiliation: Department of Biology, School of Medicine, Nara Medical University, Nara, Japan.
authors.forename: Akihisa
authors.initials: A
authors.lastname: Takahashi
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Yamakawa
authors.forename: Tadaaki
authors.initials: T
authors.lastname: Kirita
authors.forename: Katsunori
authors.initials: K
authors.lastname: Omori
authors.forename: Noriaki
authors.initials: N
authors.lastname: Ishioka
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Furusawa
authors.forename: Eiichiro
authors.initials: E
authors.lastname: Mori
authors.forename: Ken
authors.initials: K
authors.lastname: Ohnishi
authors.forename: Takeo
authors.initials: T
authors.lastname: Ohnishi
mesh_terms: D002460:Cell Line; D002467:Cell Nucleus / Q000502:physiology* / Q000528:radiation effects*; D004249:DNA Damage / Q000502:physiology*; D004307:Dose-Response Relationship, Radiation; D005347:Fibroblasts / Q000502:physiology* / Q000528:radiation effects*; D020450:Heavy Ions; D006801:Humans; D020543:Proteome / Q000378:metabolism*; D011829:Radiation Dosage
chemical_list: D020543:Proteome