Enhanced induction of abnormal telomere FISH signals in response to oxidative DNA damage.

Telomere dysfunction induces chromosomal instability, which is a driving force in the development of cancers. To examine X-irradiation's effect on telomere integrity, we investigated X-ray-induced abnormalities in telomere signals detected by fluorescence in situ hybridization (telomere FISH) in mouse embryo fibroblast cells. The abnormalities were categorized as either extra telomere signals (ETSs) or loss of telomere signals (LTSs).

High susceptibility of mouse newborns to delayed appearance of DNA double-strand breaks in neural stem/progenitor cells exposed to ionizing radiation.

Fetal brains are known to be extremely sensitive to ionizing radiation, which can induce structural and functional defects in the developing brain. However, there is less data on the effects of radiation on newborn brains. To determine the radiation sensitivity in newborn brains, we determined the number of DNA double-strand breaks (DSBs) appearing at later stage post-irradiation in neural stem/progenitor cells (NSPCs) of mouse newborns <3 days old, and compared it with the numbers of DSBs of fetal, 1-week-neonate, 2-week-neonate, and adult mice.

Repair kinetics of DNA double-strand breaks and incidence of apoptosis in mouse neural stem/progenitor cells and their differentiated neurons exposed to ionizing radiation.

Neuronal loss leads to neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease and Huntington's disease. Because of their long lifespans, neurons are assumed to possess highly efficient DNA repair ability and to be able to protect themselves from deleterious DNA damage such as DNA double-strand breaks (DSBs) produced by intrinsic and extrinsic sources. However, it remains largely unknown whether the DSB repair ability of neurons is more efficient compared with that of other cells.

A Cyclized Helix-Loop-Helix Peptide as a Molecular Scaffold for the Design of Inhibitors of Intracellular Protein-Protein Interactions by Epitope and Arginine Grafting.

The design of inhibitors of intracellular protein-protein interactions (PPIs) remains a challenge in chemical biology and drug discovery. We propose a cyclized helix-loop-helix (cHLH) peptide as a scaffold for generating cell-permeable PPI inhibitors through bifunctional grafting: epitope grafting to provide binding activity, and arginine grafting to endow cell-permeability. To inhibit p53-HDM2 interactions, the p53 epitope was grafted onto the C-terminal helix and six Arg residues were grafted onto another helix.

Growth retardation of Paramecium and mouse cells by shielding them from background radiation.

In the 1970s and 1980s, Planel et al. reported that the growth of paramecia was decreased by shielding them from background radiation. In the 1990s, Takizawa et al.

Early response of neural stem/progenitor cells after X-ray irradiation in vitro.

We investigated the effect of oxidative stress on cell cycle regulation of neural stem/progenitor cells in neurosphere culture. We exposed murine neural stem/progenitor cells to 2 Gy of X-ray irradiation at 48 h after first passage. We found that G2 and G1-arrested cells increased at 3 and 12 h after X-ray irradiation, respectively by using laser scanning cytometer.

Transcription-independent suppression of DNA synthesis by p53 in sperm-irradiated mouse zygotes.

Cell cycle arrest in response to DNA damage is important for the maintenance of genomic integrity in higher eukaryotes. We have previously reported the novel p53-dependent S-phase checkpoint operating in mouse zygotes fertilized with irradiated sperm. In the present study, we analysed the detail of the p53 function required for this S-phase checkpoint in mouse zygotes.

The novel surveillance mechanism of the Trp53-dependent s-phase checkpoint ensures chromosome damage repair and preimplantation-stage development of mouse embryos fertilized with x-irradiated sperm.

Cell cycle checkpoints and apoptosis function as surveillance mechanisms in somatic tissues. However, some of these mechanisms are lacking or are restricted during the preimplantation stage. Previously, we reported the presence of a novel Trp53-dependent S-phase checkpoint that suppresses pronuclear DNA synthesis in mouse zygotes fertilized with X-irradiated sperm (sperm-irradiated zygotes) (Shimura et al.

Persistent induction of somatic reversions of the pink-eyed unstable mutation in F1 mice born to fathers irradiated at the spermatozoa stage.

Untargeted mutation and delayed mutation are features of radiation-induced genomic instability and have been studied extensively in tissue culture cells. The mouse pink-eyed unstable (p(un)) mutation is due to an intragenic duplication of the pink-eyed dilution locus and frequently reverts back to the wild type in germ cells as well as in somatic cells. The reversion event can be detected in the retinal pigment epithelium as a cluster of pigmented cells (eye spot).

p53-dependent S-phase damage checkpoint and pronuclear cross talk in mouse zygotes with X-irradiated sperm.

One difficulty in analyzing the damage response is that the effect of damage itself and that of cellular response are hard to distinguish in irradiated cells. In mouse zygotes, damage can be introduced by irradiated sperm, while damage response can be studied in the unirradiated maternal pronucleus. We have analyzed the p53-dependent damage responses in irradiated-sperm mouse zygotes and found that a p53-responsive reporter was efficiently activated in the female pronucleus.