title: Delayed activation of DNA damage checkpoint and radiation-induced genomic instability.
abstract: Ionizing radiation induces genomic instability, transmitted over many generations through the progeny of surviving cells. It is manifested as the expression of delayed effects such as delayed cell death, delayed chromosomal instability and delayed mutagenesis. Induced genomic instability exerts its delayed effects for prolonged periods of time, suggesting the presence of a mechanism by which the initial DNA damage in the surviving cells is memorized. Our recent studies have shown that transmitted memory causes delayed DNA breakage, which in turn activates DNA damage checkpoint, and is involved in delayed manifestation of genomic instability. Although the mechanism(s) involved in DNA damage memory remain to be determined, we suggest that ionizing radiation-induced mega-base deletion destabilizes chromatin structure, which can be transmitted many generations through the progeny, and is involved in initiation and perpetuation of genomic instability. The possible involvement of delayed activation of a DNA damage checkpoint in the delayed induction of genomic instability in bystander cells is also discussed.
authors.affiliation: Division of Radiation Biology, Department of Radiology and Radiation Biology, Course of Life Sciences and Radiation Research, Graduate School of Biomedical Sciences, Nagasaki University, Japan. kzsuzuki@net.nagasaki-u.ac.jp
authors.forename: Keiji
authors.initials: K
authors.lastname: Suzuki
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Ojima
authors.forename: Seiji
authors.initials: S
authors.lastname: Kodama
authors.forename: Masami
authors.initials: M
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D002450:Cell Communication; D004249:DNA Damage; D042822:Genomic Instability / Q000528:radiation effects*; D006801:Humans; D009154:Mutation; D010641:Phenotype; D015398:Signal Transduction