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研究発表を行った学会；
・Gordon conference DNA damage, Mutation & Cancer
　　2016年 3月13日〜16日（Ventura CA U.S.A.）
タイトル；Rad18 and Chk2-mediated suppression of gapped DNA formation for maintenance of genomic stability and tumor prevention.
発表者；立石 智　氏
　　　（熊本大学　発生医学研究所　損傷修復分野）
要旨；
Introduction
When cells are irradiated with UV light, Rad18 is recruited to stalled replication fork and guide polymerase  as a molecular chaperone of the polymerase. Rad18 then functions as an ubiquitin ligase for PCNA for promoting translesion synthesis executed by polymerase. As activation of Chk2 is noticeable following UV irradiation especially in Rad18-null cells, we speculated that activated Chk2 compensate for deficiency of Rad18. Thus we have prepared Rad18-/- Chk2-/- mice to examine functions of Rad18 and Chk2 in maintenance of genome integrity and for tumor prevention.

Summary
Rad18-/- Chk2-/- mice were prone to form spontaneous spleen lymphoma while neither Rad18-/- mice nor Chk2-/- mice developed the tumors, indicating both genes contribute to tumor prevention. To investigate the mechanism of maintenance of genome integrity by Rad18 and Chk2, we prepared WT, Rad18-/-, Chk2-/- or Rad18-/-Chk2-/- ES cells from the mice. Rad18-/-Chk2-/- cells showed various chromosomal aberrations in unperturbed conditions. Reportedly Chk2 induces apoptosis and cell cycle checkpoint in response to ionizing radiation, we thus examined it using ES cells after UV irradiation. Rad18-/- cells were most sensitive to UV irradiation among the ES cells while loss of Chk2 conferred resistance on the cells. SubG1 population analysis also indicated that Chk2 induces cell death, especially in Rad18-/- cells. Similar to the cell death, G1/S checkpoint was most noticeable in Rad18-/- cells while it was abrogated by loss of Chk2. These results indicate that Chk2 induced cell death and G1/S checkpoint especially in Rad18-/- cells. Furthermore, the rate of spontaneous sister chromatid exchange (SCE) in Rad18-/-Chk2-/- cells was statistically higher than those of WT cells. Collectively, these results suggest that when Rad18 does not work well, Chk2 will be activated to induce cell death and G1/S checkpoint to prevent unfavorable events such as chromosomal abnormality and SCE. This will contribute to prevent tumorigenesis.