The Mre11 complex and ATM: a two-way functional interaction in recognising and signaling DNA double strand breaks

Mutations in components of the Mre 11/Rad50/Nbs1 complex give rise to genetic disorders characterized by neurological abnormalities, radiosensitivity, cell cycle checkpoint defects, genomic instability and cancer predisposition. Evidence exists that this complex associates with chromatin during DNA replication and acts as a sensor of double strand breaks (dsbs) in DNA after exposure to radiation. A series of recent reports provides additional support that the complex senses breaks in DNA and relays this information to ATM, mutated in ataxia-telangiectasia (A-T), which in turn activates pathways for cell cycle checkpoint activation. Paradoxically members of the Mre11 complex are also downstream of ATM in these pathways. Here, Lavin attempts to make sense of this sensing mechanism with reference to a series of recent reports on the topic. (C) 2004 Elsevier B.V. All rights reserved.

ATM signaling and genornic stability in response to DNA damage

DNA double strand breaks represent the most threatening lesion to the integrity of the genome in cells exposed to ionizing radiation and radiomimetic chemicals. Those breaks are recognized, signaled to cell cycle checkpoints and repaired by protein complexes. The product of the gene (ATM) mutated in the human genetic disorder ataxia-telangietasia (A-T) plays a central role in the recognition and signaling of DNA damage. ATM is one of an ever growing number of proteins which when mutated compromise the stability of the genome and predispose to tumour development. for recognising double strand breaks in DNA, maintaining genome stability and minimizing risk of cancer are discussed. (C) 2004 Published by Elsevier B.V.

Live cell imaging of heavy-ion-induced radiation responses by beamline microscopy

To study the dynamics of protein recruitment to DNA lesions, ion beams can be used to generate extremely localized DNA damage within restricted regions of the nuclei. This inhomogeneous spatial distribution of lesions can be visualized indirectly and rapidly in the form of radiation-induced foci using immunocytochemical detection or GFP-tagged DNA repair proteins. To analyze faster protein translocations and a possible contribution of radiation-induced chromatin movement in DNA damage recognition in live cells, we developed a remote-controlled system to obtain high-resolution fluorescence images of living cells during ion irradiation with a frame rate of the order of seconds. Using scratch replication labeling, only minor chromatin movement at sites of ion traversal was observed within the first few minutes of impact. Furthermore, time-lapse images of the GFP-coupled DNA repair protein aprataxin revealed accumulations within seconds at sites of ion hits, indicating a very fast recruitment to damaged sites. Repositioning of the irradiated cells after fixation allowed the comparison of live cell observation with immunocytochemical staining and retrospective etching of ion tracks. These results demonstrate that heavy-ion radiation-induced changes in sub-nuclear structures can be used to determine the kinetics of early protein recruitment in living cells and that the changes are not dependent on large-scale chromatin movement at short times postirradiation. © 2005 by Radiation Research Society.

Impact of changes in natural ultraviolet radiation on pigment composition, physiological and morphological characteristics of the Antarctic moss, Grimmia antarctici

The impact of ambient ultraviolet (UV)-B radiation on the endemic bryophyte, Grimmia antarctici, was studied over 14 months in East Antarctica. Over recent decades, Antarctic plants have been exposed to the largest relative increase in UV-B exposure as a result of ozone depletion. We investigated the effect of reduced UV and visible radiation on the pigment concentrations, surface reflectance and physiological and morphological parameters of this moss. Plexiglass screens were used to provide both reduced UV levels (77%) and a 50% decrease in total radiation. The screen combinations were used to separate UV photoprotective from visible photoprotective strategies, because these bryophytes are growing in relatively high light environments compared with many mosses. G. antarctici was affected negatively by ambient levels of UV radiation. Chlorophyll content was significantly lower in plants grown under near-ambient UV, while the relative proportions of photoprotective carotenoids, especially beta-carotene and zeaxanthin, increased. However, no evidence for the accumulation of UV-B-absorbing pigments in response to UV radiation was observed. Although photosynthetic rates were not affected, there was evidence of UV effects on morphology. Plants that were shaded showed fewer treatment responses and these were similar to the natural variation observed between moss growing on exposed microtopographical ridges and in more sheltered valleys within the turf. Given that other Antarctic bryophytes possess UV-B-absorbing pigments which should offer better protection under ambient UV-B radiation, these findings suggest that G. antarctici may be disadvantaged in some settings under a climate with continuing high levels of springtime UV-B radiation.