Nuclear localization of mouse Ku70 in interphase cells and focus formation ofmouse Ku70 at DNA damage sites immediately after irradiation

Journal of Veterinary Medical Science

Yasutomo YUTOKU²  Aki KOIKE²  Manabu KOIKE¹ 

[1] Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, 4�?9�?1 Anagawa, Inage-ku, Chiba 263�?8555, Japan;Radiation Risk Reduction Research, National Institute of Radiological Sciences, 4�?9�?1 Anagawa, Inage-ku, Chiba 263�?8555, Japan

关键词: DNA damage;    Ku70;    Ku80;    mouse;    nuclear localization;   

DOI  :  10.1292/jvms.14-0651

学科分类：兽医学

来源: Japanese Society of Veterinary Science

【 摘 要 】

References(24)To elucidate the mechanisms of DNA repair pathway is critical for developingnext-generation radiotherapies and chemotherapeutic drugs for cancer. Ionizing radiationand many chemotherapeutic drugs kill tumor cells mainly by inducing DNA double-strandbreaks (DSBs). The classical nonhomologous DNA-end joining (NHEJ) (C-NHEJ) pathway repairsa predominant fraction of DSBs in mammalian cells. The C-NHEJ pathway appears to startwith the binding of Ku (heterodimer of Ku70 and Ku80) to DNA break ends. Therefore,recruitment of Ku to DSB sites might play a critical role in regulating NHEJ activity.Indeed, human Ku70 and Ku80 localize in the nuclei and accumulate at microirradiated DSBsites. However, the localization and regulation mechanisms of Ku70 and Ku80 homologues inanimal models, such as mice and other species, have not been elucidated in detail,particularly in cells immediately after microirradiation. Here, we show that EYFP-taggedmouse Ku70 localizes in the interphase nuclei of mouse fibroblasts and epithelial cells.Furthermore, our findings indicate that EYFP-mouse Ku70 accumulates with its heterodimericpartner Ku80 immediately at laser-microirradiated DSB sites. We also confirmed that thestructure of Ku70 nuclear localization signal (NLS) is highly conserved among variousrodent species, such as the mouse, rat, degu and ground squirrel, supporting the idea thatNLS is important for the regulation of rodent Ku70 function. Collectively, these resultssuggest that the mechanisms of regulating the localization and accumulation of Ku70 atDSBs might be well conserved between the mouse and human species.

【 授权许可】

Unknown