|
The 56th Annual Meeting of Radiation Research Society, RRS2010, was taken place between September 25 and 29, 2010, in Maui, Hawaii. As it was in Hawaii, more people were expected to participate to the meeting from Japan. In fact, two symposia were recommended by the Japanese Radiation Research Society members, and I gave a talk in one of the two symposia. Nineteen symposia, topical review and minisymposia were organized in the morning sessions, and poster sessions were in the afternoon. Particularly, more than 600 titles were presented in the poster sessions, and it was quite impressive as many of the presenters are young scientists and graduate students.
During the meeting, various aspects of radiation effects were discussed, those include the initial radiation steps, bystander effects, low-dose and low-dose rate effects, and space radiation. Especially, multiple sessions discussed on the physiological significance of bystander effects. However, more confusion could be the right word to describe current situation. While more molecular mechanisms were proposed, its biological significance became more and more obscure. There was no consensus on the role of bystander effects on radiation risk assessment. It seemed that bystander effects, and other so-called non-targeted effects should be studied in appropriate radiation-induced carcinogenesis models. As bystander effects are able to induce both cell death and genome instability, experimental systems, which mimic radiation-induced carcinogenesis in vivo, are indispensable. In addition, we do need experimental systems with stem cells.
In this meeting, we introduced our recent study towards a role of higher-order chromatin structure on DNA damage checkpoint signaling. It is well established that ATM-dependent DNA damage signal is amplified by recruiting DNA damage checkpoint factors to the chromatin regions neighboring DNA double strand breaks. ATM-dependent phosphorylation of histone H2AX at serine 139 is the primary modification, which facilitates the subsequent formation of large protein complex detected as radiation-induced discrete foci. Using a specific inhibitor of ATM, we proved that the initial ATM-dependent step was followed by the ATM-independent step. The latter step was expected to be dependent upon histone modifications other than phosphorylation. So far, ubiquitination, sumoylation, acetylation, and methylation have been reported as modifications of histone H2AX and H2A. However, all these modifications requires ATM-dependent phosphorylation of histone H2AX. Therefore, we planned to investigate modifications of other histones, such as histone H3 and H4. Previously, it was reported that dimethylation of histone H3 at K79 or dimethylation of histone H4 at K20 were involved in 53BP1 foci formation, however, role of these modifications remained to be determined. Our strategy was to survey related enzymes using chemical inhibitors. As a result, we found that p300/CBP required not for the initial but for the delayed foci formation. We also demonstrated that G9a, which catalyzes dimethylation of histone H3 at K9, played a crucial role in 53BP1 foci formation. In fact, G9a was recruited to the subnuclear regions with DSBs. A knockdown of G9a with shRNA compromised residual 53BP1 foci. Thus, our results suggest, for the first time, that dimethylation of histone H3 by a novel histone methylase, G9a, could be the indispensable modification required for the foci formation.
Many critical questions in radiation health effects are still remained to be addressed. A few big projects in US may be the clue to solve these questions, however, a lack of ideal experimental models seems to be crucial. To establish global strategic center for radiation health risk control we need further acceleration of communications between the scientists and international collaborations. This should be the way to achieve our objectives.
|
